by

Tom Swartz

This issue's Clinical Trail News column is dedicated to Phase I, II and III clinical trials dealing with Rhabdomyosarcoma.  Many of the entries are international in scope.

Clinical Trials Currently Recruiting Patients

Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma. This Phase III study is currently recruiting patients. The purpose of this trial is to compare the effectiveness of chemotherapy with or without radiation therapy in treating patients who have newly-diagnosed rhabdomyosarcoma.  Patients are assigned to 1 of 2 groups, depending on histology and site of disease.  In Group I patients receive:  vincristine IV over 1 minute weekly for 8 weeks and dactinomycin IV over 1 minute once every 3 weeks for 4 doses. Treatment repeats every 12 weeks for 4 courses. Radiotherapy is administered to patients with clinical group II or III disease on weeks 3-8.  In Group II patients receive: vincristine and dactinomycin as in group I. Patients also receive cyclophosphamide IV over 30-60 minutes and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously once daily beginning 24 hours after completion of chemotherapy and continuing for 10 days or until blood counts recover. Radiotherapy is administered on weeks 3-8, 12-17, or 28-33, if clinically indicated as in group I. Patients are followed every 3-4 months for 3 years (4 years after diagnosis), every 6 months for 1 year, and then annually thereafter. A total of 254 patients for group I will be accrued for this study within 6 years. Approximately 12 patients per year will be accrued for group II.  Patients under 50 years of age are eligible. This is a multicenter study, which includes centers in Canada, Australia, New Zealand, Netherlands, and Switzerland. 

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma. This Phase III study is currently recruiting patients.  The purpose of this trial is to compare the effectiveness of two combination chemotherapy regimens in treating patients who have previously untreated rhabdomyosarcoma or sarcoma.  Patients are stratified according to disease (embryonal histology, stage II or III, Clinical Group III vs. embryonal histology, Clinical Group IV, less than 10 years of age vs. alveolar or undifferentiated sarcoma histology, stage I, Clinical Group I vs. alveolar or undifferentiated sarcoma histology, stage II or III, Clinical Group II or III). Patients are randomized to 1 of 2 treatment arms: 

Arm I: Patients receive vincristine IV over 5-10 minutes once a week on weeks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV is administered over 15-20 minutes once a week on weeks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV is administered over 30-60 minutes once a week on weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After the initial 12 weeks of chemotherapy, depending on tumor shrinkage, patients may undergo surgery. After recovery from surgery, patients receive radiotherapy once a day, 5 days a week, during weeks 12-18. For patients receiving radiotherapy during weeks 0-6, dactinomycin is omitted during weeks 3 and 6 and administered during weeks 15 and 18. For patients receiving radiotherapy during weeks 12-18, dactinomycin is omitted during weeks 15 and 18. Patients showing an adequate response at week 24 continue chemotherapy during weeks 24-39. Patients with Clinical Group III tumors of a parameningeal site with documented evidence of intracranial extension receive radiotherapy within the first 2 weeks of the initiation of the first course of chemotherapy (day 0).

Patients with Clinical Group II parameningeal tumors and Clinical Group III parameningeal tumors with base of skull erosion and/or cranial nerve palsy without evidence of intracranial extension receive radiotherapy on week 12 (day 84) or immediately thereafter.

Patients with Clinical Group IV parameningeal tumors with distant metastases receive radiotherapy to the primary site on week 12 (day 84). Patients with distant metastases confined to one site may receive radiotherapy to the metastatic site concurrently with therapy to the primary site if it began within 2 weeks of the initiation of chemotherapy (day 0).

Arm II: Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.

A total of 518 patients will be accrued for this study. Patients under 50 years of age are eligible. This is a multicenter study, which includes centers in Canada, Australia, New Zealand, Netherlands, and Switzerland. 

Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Metastatic Rhabdomyosarcoma or Sarcoma. This Phase II study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combination chemotherapy combined with radiation therapy in treating patients who have metastatic rhabdomyosarcoma or sarcoma.  The treatment outline for this study is as follows:

	Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 60 minutes on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2 courses. Patients experiencing partial or complete response proceed to regimen A. Patients experiencing stable or progressive disease proceed to regimen B.
	Regimen A: Patients receive vincristine IV over 1 minute weekly on weeks 6-13, 15-19, 23-27, 29, 32-35, 38-39, and 41; dactinomycin IV over 1 minute weekly on weeks 6, 12, 23, 29, 35, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 12, 16, 19, 23, 29, 35, and 41. Patients also receive irinotecan IV over 1 hour daily, 5 days a week, on weeks 9, 10, 26, 27, 32, 33, 38, and 39 and undergo radiotherapy daily, 5 days a week, on weeks 15-22.
	Regimen B: Patients receive vincristine as in regimen A; dactinomycin IV over 1 minute weekly on weeks 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41 and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients receive radiotherapy as in regimen A. Patients who do not receive upfront window irinotecan/vincristine therapy are treated with standard therapy.
	Patients receive vincristine IV over 1 minute weekly on weeks 0-13, 15-19, 23-27, 29, 32-35, 38, and 41; dactinomycin IV over 1 minute weekly on weeks 0, 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 0, 3, 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients without evidence of intracranial extension receive radiotherapy once daily, 5 days a week, during weeks 15-22. Patients with evidence of intracranial extension, or who require emergency radiotherapy, receive radiotherapy during weeks 0-6. Dactinomycin is withheld during radiotherapy. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) beginning 24 hours after completion of each course of chemotherapy and continuing until blood counts recover. Alternatively, patients may receive pegfilgrastim SC beginning 24-36 hours after completion of each course of chemotherapy and continuing until blood counts recover.

A total of 18-46 patients will be accrued for this study. Patients under 50 years of age are eligible. This is a multicenter study, which includes centers in Canada, Australia, New Zealand, Netherlands, and Switzerland.

Comparison of Chemotherapy Regimens in Treating Children With Relapsed or Progressive Rhabdomyosarcoma. This Phase II study is currently recruiting patients.  The purpose of this trial is to compare the effectiveness of different combination chemotherapy regimens in treating children who have rhabdomyosarcoma.  Patients are stratified according to risk status and window therapy eligibility (unfavorable risk and eligible vs. unfavorable risk and ineligible vs. favorable risk).  The treatment outline for this study is as follows:

	Patients are stratified according to prior topotecan (yes vs. no). These patients are randomized to 1 of 2 treatment arms.
	Arm I: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
	Arm II: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
	Patients in both arms with partial response (PR) or complete response (CR) receive 5 additional courses of irinotecan and vincristine on the previous schedule. In addition, patients with PR or CR also receive cyclophosphamide/doxorubicin (CD) and ifosfamide/etoposide (IE) chemotherapy.
	CD/IE Chemotherapy: Patients receive cyclophosphamide IV over 1 hour and doxorubicin IV over 15-60 minutes on day 1 of weeks 7, 16, 28, 37, and 40. Patients also receive ifosfamide IV over 1 hour and etoposide IV on days 1-5 of weeks 10, 19, 22, 31, and 43. Treatment continues in the absence of disease progression or unacceptable toxicity.
	Patients with no response or progressive disease on arm I or II proceed to tirapazamine/cyclophosphamide/doxorubicin (TCD) and ifosfamide/etoposide (IE) chemotherapy.
	TCD/IE Chemotherapy: Patients receive tirapazamine IV over 2 hours, cyclophosphamide IV over 1 hour, and doxorubicin IV over 15-60 minutes on day 1 of weeks 7, 10, 16, 25, and 34. Patients also receive ifosfamide IV over 1 hour and etoposide IV on days 1-5 of weeks 13, 19, 22, 28, 31, and 37.
	Patients with unfavorable risk and ineligible for window therapy: Patients receive tirapazamine IV over 2 hours, cyclophosphamide IV over 1 hour, and doxorubicin IV over 15-60 minutes on day 1 of weeks 1, 4, 10, 19, and 28. Patients also receive ifosfamide IV over 1 hour and etoposide IV on days 1-5 of weeks 7, 13, 16, 22, 25, and 31. Patients also receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) beginning 1 day after each course of chemotherapy and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.
	Patients with favorable risk: Patients receive cyclophosphamide IV over 1 hour and doxorubicin IV over 15-60 minutes on day 1 of weeks 1, 4, 10, 19, and 28. Patients also receive ifosfamide IV over 1 hour and etoposide IV on days 1-5 of weeks 7, 13, 16, 22, 25, and 31. Patients also receive G-CSF or GM-CSF SC beginning 1 day after each course of chemotherapy and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter.

A total of 102-120 patients with unfavorable-risk disease (51 per treatment arm), and a total of 20-30 patients with favorable-risk disease will be accrued for this study.  Patients under 21 years of age are eligible.  This is a multicenter study, which includes centers in Canada, Australia, New Zealand, Netherlands, and Switzerland.

Irinotecan and Carboplatin as Upfront Window Therapy in Treating Patients With Newly Diagnosed Intermediate-Risk or High-Risk Rhabdomyosarcoma. This Phase II study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of irinotecan and carboplatin as a first-line therapy in treating patients who have newly diagnosed intermediate-risk or high-risk rhabdomyosarcoma.  The treatment outline for this study is as follows:

	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on day 1 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2 courses.
	Patients receive vincristine IV on days 1, 8, and 15; dexrazoxane IV over 15-30 minutes, doxorubicin IV over 15-30 minutes, and cyclophosphamide IV over 1 hour on days 1 and 2; and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on approximately day 3 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 3 courses. Some patients may undergo surgical resection of the tumor after completion of course 5. After course 5, patients undergo radiotherapy once daily, 5 days a week, for 4-5.5 weeks.
	Patients receive vincristine IV and carboplatin IV over 1 hour on day 1; irinotecan IV over 1 hour on days 1-5 and 8-12; and G-CSF SC once daily beginning on approximately day 13 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses. NOTE: *Patients who develop disease progression during courses 1 or 2 do not receive further irinotecan and carboplatin. Instead, patients receive ifosfamide and etoposide as in courses 8 and 9.
	Courses 8 and 9: Patients receive vincristine IV on day 1; etoposide IV over 1 hour and ifosfamide IV over 2 hours on days 1-5; and G-CSF SC once daily beginning on approximately day 6 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses.
	Course 10: Patients receive vincristine IV on days 1, 8, 15, 22, 29, 36, and 43; dexrazoxane IV over 15-30 minutes, doxorubicin IV over 15-30 minutes, and cyclophosphamide IV over 1 hour on days 1 and 2; and filgrastim SC beginning on approximately day 3 and continuing until blood counts recover (1 course).
	Patients receive etoposide IV over 1 hour and ifosfamide IV over 2 hours on days 1-5 and G-CSF SC once daily beginning on approximately day 6 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses. Patients with high-risk disease proceed to maintenance therapy.
	Patients receive irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 6 courses. NOTE: *Patients who develop disease progression during courses 1 or 2 do not receive further irinotecan.

In all courses, treatment continues in the absence of unacceptable toxicity or disease progression or recurrence after initial response.  A total of 24-61 patients will be accrued for this study.  Patients 30 years old and under are eligible.  This study is being conducted at Memorial Sloan-Kettering Cancer Center, New York.

Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors. This Phase II study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combination chemotherapy in treating children with metastatic rhabdomyosarcoma or other malignant mesenchymal tumors.  Patients are stratified according to risk group (standard vs. high).  The treatment outline for this study is as follows:

Standard-risk patients:

Initial chemotherapy: Patients receive vincristine IV on day 1 for weeks 1-7. Patients also receive dactinomycin IV on day 1 and ifosfamide IV over 1 hour on days 1-3 of week 1. Patients then receive carboplatin IV over 1 hour and epirubicin IV over 6 hours on day 1 of week 4. Patients then receive ifosfamide IV over 1 hour and etoposide IV over 4 hours on days 1-3 of week 7. Treatment repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. After the second course, patients with less than 50% partial response (PR) are removed from study. Patients with parameningeal disease undergo radiotherapy 5 days a week for about 8 weeks beginning at week 9.

Maintenance chemotherapy: Patients receive cyclophosphamide IV over 1 hour, vincristine IV, and dactinomycin IV on day 1. Treatment repeats every 3 weeks for 9 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in PR at week 17 undergo radiotherapy for about 9 weeks beginning at week 18.

High-risk patients:

Initial chemotherapy: Patients receive window study drug carboplatin IV over 1 hour or doxorubicin on day 1. Treatment repeats every 3 weeks for 2 courses. Patients receive high-dose cyclophosphamide IV over 1 hour on days 1-3 of week 7. Beginning on day 8, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) daily until day 13. Patients may undergo peripheral blood stem cell (PBSC) collection. Patients receive high-dose etoposide IV over 24 hours on days 15-17. Beginning on day 22, patients receive G-CSF IV or SC daily until day 27. Patients receive high-dose cyclophosphamide IV over 1 hour on days 29-31. Beginning on day 36, patients receive G-CSF IV or SC daily until day 42. Patients may undergo PBSC collection if not previously performed. Patients who achieve complete response (CR) are removed from study. Patients receive high-dose carboplatin IV over 1 hour on days 44-48. Patients undergo PBSC reinfusion on day 52. Beginning on day 55, patients receive G-CSF IV or SC daily until blood counts recover.

Maintenance chemotherapy: Patients receive maintenance chemotherapy comprising cyclophosphamide, vincristine, and dactinomycin in the same manner as the standard-risk patients. Patients with parameningeal disease and those not achieving CR undergo radiotherapy beginning at week 17. Patients achieving CR, unless metastatic disease is resected, undergo radiotherapy beginning on week 15. A total of 8-30 standard-risk patients and 15-75 high-risk patients will be accrued for this study.  Patients 6 months to 17 years of age are eligible.  This study is being conducted at centers in France, Ireland, and the United Kingdom.

Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma. This diagnostic study is currently recruiting patients. The purpose of this study is to perform genetic testing on children with soft tissue sarcoma or rhabdomyosarcoma to identify children who are at risk of developing leukemia from the chemotherapy used to treat sarcoma.  Blood is collected from patients at diagnosis (preferably before chemotherapy or transfusion), at end of therapy, and at 6 months, 1 year, 2 years, and 3 years after therapy.  Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.  A total of 321 patients will be accrued for this study.  Patients up to 17 years of age are eligible.  This is a multicenter study, which includes centers in Canada, Australia, New Zealand, Netherlands, and Switzerland.

Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma. This Phase III study is currently recruiting patients. The purpose of this study is to study the effectiveness of different regimens of combination chemotherapy with or without surgery and/or radiation therapy in treating patients with soft tissue sarcoma.  This is a randomized study for patients with high-risk, nonmetastatic sarcoma. Patients are stratified according to disease type (rhabdomyosarcoma (RMS) vs. non-RMS disease) and parameningeal site of disease.  Patients with RMS are further randomized by alveolar histology.   Randomization occurs after the first course of chemotherapy.  All patients, regardless of disease stage, are registered to this study and outcome is followed, although patients with metastatic RMS or non-RMS malignant mesenchymal tumors are referred for treatment on another study.  Patients diagnosed more than 8 weeks prior to entry or who are unavailable for follow-up are not treated on study. Doses are modified for patients under 1 year of age or under 10 kg of body weight.  All other patients are assigned therapy based on risk group.  After surgery, patients with complete resection and with proven or possible chemosensitive histologies proceed to chemotherapy on a low-risk regimen.  Patients with questionable completeness of resection proceed to chemotherapy for standard-risk or high-risk tumors, as appropriate.  A total of 400 patients will be accrued for this study.  Patients up to 17 years of age are eligible.  The location of this study is at the Institute of Child Health, Bristol, England.

Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors. This Phase I study is currently recruiting patients.  The purpose of this study is to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.  Patients undergo surgery for diagnosis and maximal tumor resection.  Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.  Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.  A total of 83 patients will be accrued for this study.  Patients 6 months to less than 3 years of age are eligible.  This is a multicenter study, which includes centers in Canada, Australia, and New Zealand.

Irinotecan in Treating Children With Refractory Solid Tumors

This Phase II study is currently recruiting patients. The purpose of the study is to study the effectiveness of irinotecan in treating children who have refractory solid tumors, including rhabdomyosarcoma.  Patients are stratified according to type of solid tumor or brain tumor. Patients receive irinotecan IV over 60 minutes on days 1-5.  Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.  A total of 225 patients will be accrued for this study.  Patients 1 to 21 years of age are eligible. This is a multicenter study, which includes centers in Canada, Australia, New Zealand, Netherlands, and Switzerland. 

Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts after Intensive Chemotherapy. This Phase I study is currently recruiting patients.  Filgrastim (granulocyte colony-stimulating factor) shortens the duration of chemotherapy-induced neutropenia and lowers the risk of infection.  It is administered by daily subcutaneous injection after cytotoxic chemotherapy in children treated with dose-intensive chemotherapy, and has become a standard component of the treatment regimen. Filgrastim-SD/01 is a sustained duration form of Filgrastim.  In phase I and phase II trials in adults, a single dose of Filgrastim-SD/01 appears to be equivalent to daily dosing of Filgrastim in enhancing neutrophil recovery and has a comparable adverse event profile.  The purpose of this trial is to compare the tolerance, toxicity, and therapeutic effects of Filgrastim-SD/01 given as a single injection after chemotherapy to daily subcutaneous Filgrastim in patients with newly diagnosed sarcoma, including rhabdomyosarcoma.  The pharmacokinetics of Filgrastim-SD/01 will also be compared to the pharmacokinetics of Filgrastim. This trial will also be a platform for performing biological studies of these tumors and for detailed cardiac studies. High-risk patients who are treated on this front line trial and respond will also be candidates for a planned transplant protocol.  A total of 34 patients (17 patients per treatment arm) will be recruited.  Patients 25 years of age or less at the time of diagnosis are eligible.  The location of this study is at the National Cancer Institute, Bethesda, Maryland.

P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors. This Phase I study is currently recruiting patients.  This study will examine the safety and side effects of tariquidar in children and adolescents with cancer and test whether it can improve current anticancer drug treatments.  Studies have found that a protein (P-glycoprotein) on some cancer cells pumps anticancer drugs out of the cells, reducing treatment effectiveness.  In laboratory tests, an experimental drug called tariquidar has blocked pumping by this protein. Tariquidar is being used in this study to try to increase amounts of the anticancer drugs vinorelbine (Navelbinea), doxorubicin (Adriamycin) or docetaxel (Taxotere) in cancer cells.  Patients between 2 and 18 years of age with solid tumors, including rhabdomyosarcoma, who have relapsed or who do not respond to frontline therapy and have no other treatment options may be eligible for this study.  Participants will receive tariquidar plus either doxorubicin, vinorelbine or docetaxel, depending on the type of cancer, previous treatments, and side effects of prior treatment.  Treatment will be given in 21-day cycles for no more than eight cycles.  The expected total enrollment is 36 patients.  The location of this study is at the National Cancer Institute, Bethesda, Maryland.

Temozolomide and O6-Benzylguanine for Treating Childhood Cancers. This Phase I study is currently recruiting patients.  This study will investigate the combined use of temozolomide (TMZ) and O6-benzylguanine (O6BG) for treating cancer. TMZ is an anti-cancer drug approved to treat certain brain tumors in adults. TMZ loses its effectiveness over time because a protein called AGT makes the tumor resistant to the drug. O6BG inactivates AGT and, therefore, may prolong TMZ's effectiveness.  Children and young adults under age 21 with various types of cancer, including rhabdomyosarcoma, for whom standard treatment was not successful may be eligible for this study.  Participants will receive TMZ capsules by mouth and an intravenous infusion of O6BG 5 days in a row every month for up to 12 months. Blood will be drawn on days 3 and 5 of the first course of treatment to measure AGT levels. Also on day 5 of the first treatment course, 16 blood samples (1 teaspoon each) will be taken over a 48-hour period to study how the two drugs work in the body. If possible, a heparin lock will be placed in the vein to avoid having multiple needle sticks. A tissue biopsy (removal of a small piece of tumor) may be taken if the tumor is close to the skin and not near a vital organ. The sample will be used to evaluate the effect of O6BG on AGT levels.  A total of 48 patients will be recruited.  The location of this study is at the National Cancer Institute, Bethesda, Maryland.

Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors. This Phase II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of arsenic trioxide in treating children who have advanced neuroblastoma or other solid tumors (including rhabdomyosarcoma).  Patients are stratified according to type of disease.  Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.  Patients are followed every 2-3 months for 1 year and then annually thereafter.  A total of 45-120 patients (15-40 per stratum) will be accrued for this study.  Patients 40 years of age and under are eligible.  The location of this study is at Memorial Sloan-Kettering Cancer Center, New York.

Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases. This Phase II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of umbilical cord blood as a source of stem cells in treating young patients who have cancer (including rhabdomyosarcoma) or other diseases.  Patients are treated on 1 of 3 preparative therapy regimens.  In Regimen A: Patients undergo total body irradiation (TBI) three times daily on days -7 to -4. Patients receive cyclophosphamide IV over 30-60 minutes on days -3 and -2 and anti-thymocyte globulin (ATG) IV over at least 6 hours on days -3 to -1.  In Regimen B (patients who do not receive TBI): Patients receive oral busulfan 4 times daily on days -8 to -5 and ATG IV over at least 6 hours and melphalan IV over 15-20 minutes on days -4 to -2.  In Regimen C (patients with Fanconi's anemia and related disorders): Patients undergo TBI on day -6. Patients receive ATG IV over at least 6 hours and methylprednisolone IV on days -5 to -1 and fludarabine IV over 30 minutes and cyclophosphamide IV over 30-60 minutes on days -5 to -2.  Cord blood transplantation: All patients undergo umbilical cord blood transplantation on day 0.  Post-transplantation therapy: Patients receive oral or IV cyclosporine over 1 hour daily beginning on day -1 and continuing through day 183. Patients receive oral or IV methylprednisolone twice daily on days 5-27 and once daily beginning on day 28 and continuing until attending physician decides to terminate the use of this drug.  Patients receive filgrastim (G-CSF) IV on days 7, 8 and 9.  A total of 25 patients will be accrued for this study.  Patients 21 years of age and under are eligible.  This study is being conducted at the Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania.

Stem Cell Transplantation in Patients with High-Risk and Recurrent Pediatric Sarcomas. This Phase I trial is currently recruiting patients.  This study will examine the safety and effectiveness of stem cell transplantation for treating patients with sarcomas, including rhabdomyosarcoma.  Stem cells are immature cells in the bone marrow and blood stream that develop into blood cells. In patients with certain cancers, stem cells transplanted from a healthy donor travel to the patient's bone marrow and begin producing normal cells. In addition, the donor's immune cells attack the patient's cancer cells in what is called a graft-versus-tumor effect, contributing to cure of the disease. This study will determine whether this treatment can be used successfully to treat patients with sarcomas.  Patients between 5 and 29 years of age with a sarcoma that has spread from the primary site or cannot be removed surgically, and for whom effective treatment is not available, may be eligible for this study. Candidates must have a matched donor (usually a sibling). Participants will undergo the following procedures: Donors - Stem cells are collected from the donor. To do this, the hormone G-CSF is injected under the skin for several days to move stem cells out of the bone marrow into the bloodstream. Then, the cells are collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the stem cells are separated out and removed. The rest of the blood is returned to the donor through a needle in the other arm.  Patients - Before the transplant procedure, patients receive from one to three cycles of induction chemotherapy, with each cycle consisting of 5 days of fludarabine, cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone followed by at least a 17-day rest period.  After the induction therapy, the patient is admitted to the hospital for 4 days of chemotherapy with high doses of cyclophosphamide, melphalan, and fludarabine. Three days later, the stem cells are infused. The anticipated hospital stay is about 3 weeks, but may be longer if complications arise. Patients are discharged when their white cell count is near normal, they have no fever or infection, they can take sufficient food and fluids by mouth, and they have no signs of serious graft-versus-host disease (GVHD)-a condition in which the donor's cells see the patient's cells as foreign and mount an immune response against them.  After hospital discharge, patients are followed in the clinic at least once or twice weekly for a medical history, physical exam, and blood tests. They receive medications to prevent infection and GVHD and, if needed, blood transfusions. After the first 100 days, the risk of serious complications decreases and follow-up visits may be less frequent. Follow-up continues for at least 5 years. During the course of the study, patients undergo repeated medical evaluations, including blood tests and bone marrow aspirations, to check on the cancer and on any treatment side effects. On four occasions, white blood cells are collected through apheresis to see if immune responses can be generated against the sarcomas treated in this study. Positron emission tomography (PET) scans are done on five occasions.  The expected total enrollment is 76 patients.  This study is being conducted at the National Cancer Institute, Bethesda, Maryland.  

Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors. This Phase I/II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of temozolomide plus peripheral stem cell transplantation in treating children who have newly diagnosed malignant glioma or recurrent central nervous system tumors or other solid tumors, including rhabdomyosarcoma.  Patients receive filgrastim (G-CSF) subcutaneously or IV beginning on day -5 and continuing through at least day 3.  Peripheral blood stem cells (PBSC) are collected on days 0, 2, and 4.  Patients then receive oral temozolomide daily for 5 consecutive days. PBSC collections are reinfused 1 day after the last dose of temozolomide.  Patients also receive G-CSF beginning at the time of transplant and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.  Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicities.  Patients are followed every 3 months for 1-3 years, then annually thereafter.  A total of 30 patients will be accrued for this study.  Patients 18 years of age and under are eligible.  This study is being conducted at the Duke Comprehensive Cancer Center, Durham, North Carolina.

ABT-751 in Treating Young Patients With Refractory Solid Tumors. This Phase I trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of ABT-751 in treating young patients who have refractory solid tumors, including rhabdomyosarcoma.  This is an open-label, dose-escalation study of 2 different schedules of ABT-751. Patients are assigned to 1 of 2 dosing schedules.  In Schedule 1: Patients receive oral ABT-751 once daily on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.  In Schedule 2: Patients receive oral ABT-751 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. On each schedule, cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 9 patients (a minimum of 3 patients age 11 and under and 3 patients age 12 to 18) are treated at the MTD.  A maximum of 48 patients (24 per dosing schedule) will be accrued for this study.  Patients 18 years of age and under are eligible.  This study is being conducted at centers in Illinois, Maryland, and Pennsylvania.  

Erlotinib and Temozolomide in Treating Young Patients With Recurrent or Refractory Solid Tumors. This Phase I trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combining erlotinib with temozolomide in treating young patients who have recurrent or refractory solid tumors, including rhabdomyosarcoma.  This is a multicenter, dose-escalation study of erlotinib. Patients are stratified according to pretreatment (heavily pretreated vs. less heavily pretreated).  Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.  Cohorts of 3-6 patients receive escalating doses of erlotinib during course 1 only until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.  A total of 9-24 patients will be accrued for this study.  Patients 21 years of age and under are eligible.  This is a multicenter study, which includes centers in Canada.

Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma. This Phase III trial is currently recruiting patients.  The purpose of this trial is to compare the effectiveness of combination chemotherapy with or without hyperthermia therapy in treating patients with soft tissue sarcoma, including rhabdomyosarcoma.  Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells.  Patients are stratified according to risk category and disease site (extremity vs. nonextremity). Patients are randomized to one of two treatment arms.  In Arm I: Patients receive etoposide IV over 30 minutes on days 1 and 4, ifosfamide IV over 60 minutes on days 1-4, and doxorubicin IV over 30 minutes on day 1. Treatment continues every 21 days for a total of 4 courses. Patients also undergo regional hyperthermia.  In Arm II: Patients receive chemotherapy alone as in arm I. Patients in both arms undergo definitive surgery 4-6 weeks after chemotherapy. Patients also undergo radiotherapy beginning 4-6 weeks after surgery. After completion of surgery and radiotherapy, patients with non-resectable tumors showing no disease progression receive an additional 4 courses of chemotherapy with or without regional hyperthermia according to above treatment schedule.  A total of 340 patients (170 patients per arm) will be accrued for this study.  Patients 18 to 70 years of age are eligible.  This study is being conducted at several centers in Germany. 

Liposomal Doxorubicin Plus Ifosfamide in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma. This Phase I trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combining liposomaldoxorubicin with ifosfamide in treating patients who have advanced or metastatic soft tissue sarcoma, including rhabdomyosarcoma.  This is a dose-escalation study of ifosfamide.  Patients receive doxorubicin HCl liposome IV over 1 hour on day 1 and ifosfamide IV over 4 hours on days 1-3 OR on days 1-4 (for patients enrolled on dose level 6). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.  Cohorts of 3-6 patients receive escalating doses of ifosfamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.  A total of 3-24 patients will be accrued for this study.  Patients 18 to 70 years of age are eligible.  This study is being conducted at centers in Denmark and Germany. ►

Exatecan Mesylate in Treating Patients With Advanced Soft Tissue Sarcoma. This Phase II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of exatecan mesylate in treating patients who have advanced soft tissue sarcoma, including rhabdomyosarcoma.  Patients are stratified according to histological diagnosis (leiomyosarcoma vs. other histologies).  Patients receive exatecan mesylate IV over 30 minutes daily on days 1-5.  Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.  A total of 32-50 patients (16-25 per stratum) will be accrued for this study.  Patients 15 to 75 years of age are eligible.  This study is being conducted at centers in Belgium, Denmark, Germany, and Slovakia.

Soblidotin in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma. This Phase II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of soblidotin in treating patients who have advanced or metastatic soft tissue sarcoma, including rhabdomyosarcoma.  Patients receive soblidotin IV over 1 hour on days 1 and 8. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.  A total of 27 patients will be accrued for this study.  Patients 15 years of age and above are eligible.  This study is being conducted at centers in Alabama, New York, and Texas.

BMS-247550 to Treat Children with Solid Tumors. This Phase I trial is currently recruiting patients.  This study will determine the highest dose of the experimental anticancer drug BMS-247550 that can be given safely to children.  It will examine how the body handles the drug, its side effects and its effect on tumors. BMS-247550 belongs to a class of drugs called epothilones.  These drugs are similar to another class called taxanes, which includes paclitaxel (Taxol) and docetaxel (Taxotere).  The epothilones are able to kill cancer cells that are resistant to Taxol.  Children 2 to 18 years of age and older with solid tumor cancers, including rhabdomyosarcoma, that do not respond to standard therapy may be eligible for this study.  Participants will receive BMS-247550 intravenously over a 60-minute period for 5 consecutive days in 21- to 28-day cycles (i.e., 5 days of drug treatment followed by 15 to 22 days without drug, depending on the amount of time needed to recover from the drug side effects). The drug dose will be increased in successive small groups of patients, if the side effects at the previous dose are acceptable, until the optimum dose is achieved. Patients may continue treatment indefinitely unless their cancer worsens or they develop side effects that persist for more than 2 weeks.  The expected total enrollment is 30 patients.  This study is being conducted at the National Cancer Institute, Bethesda, Maryland. 

Phase I Trial of ABT-751 in Children with Solid Tumors. This Phase I study is currently recruiting patients.  This study will determine the side effects and maximum tolerated dose of the experimental drug ABT-751 that can be safely given to children and young adults with solid tumors.  ABT-751 belongs to a new class of anticancer drugs that hamper the replication of cancer cells.  It works by binding to a protein called tubulin.  Other drugs that work this way include vincristine, vinblastine, vinorelbine, paclitaxel, and docetaxel.  In laboratory studies, ABT-751 kills cancer cells that are resistant to vincristine and paclitaxel.  Patients up to 18 years of age with solid tumors, including rhabdomyosarcoma, whose disease has relapsed, or whose tumor no longer responds to standard treatment, may be eligible for this study.  Participants will take one ABT-751 capsule a day for 7 days each treatment cycle.  A treatment cycle will be 21 to 28 days, depending on how long it takes the patient to recover from the drug side effects.  The drug dose will be increased gradually in successive groups of patients if side effects of the previous dose were acceptable.  Patients may continue treatment unless their disease worsens with ABT-751 or irreversible side effects occur.  Expected total enrollment is 48 patients.  This study is being conducted at the National Cancer Institute, Bethesda, Maryland.

Clinical Trials Not Yet Open 

Vincristine, Dactinomycin, Cyclophosphamide, and Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma

This Phase III study is not yet open for patient recruitment.  The purpose of this trial is to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have newly diagnosed low-risk rhabdomyosarcoma.  Patients are assigned to 1 of 2 treatment regimens according to disease stage and clinical group.  In Regimen I patients receive: VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21 and dactinomycin* IV over 1 minute on day 1 of weeks 13, 16, 19, and 22; and radiotherapy**,5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose.  In Regimen II patients receive: VAC chemotherapy and radiotherapy** as in regimen I and VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin* IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46. Patients with clinical group III disease may undergo second-look surgery at week 13 followed by response-adjusted radiotherapy, administered as in regimen I, and continued VA* chemotherapy as in regimen I or II.  In both regimens, treatment continues in the absence of disease progression or unacceptable toxicity.  A total of 360 patients will be accrued, and patients under 50 years of age are eligible.  This is a multicenter study; centers have not been identified.

Whole-Body MRI and Conventional Imaging in Detecting Distant Metastases in Young Patients With Solid Tumors or Lymphoma. This diagnostic trial is not yet open for patient recruitment.  The purpose of the trial is to compare the effectiveness of whole-body MRI with that of standard imaging procedures in detecting distant metastases in patients who have solid tumors (including rhabdomyosarcoma) or lymphoma.  Patients undergo conventional MRI, CT scan, and scintigraphy and experimental whole-body MRI sequences. Patients may optionally undergo fludeoxyglucose F18 positron emission tomography (FDG-PET).  Patients with a lesion (or lesions) detected on whole-body MRI or FDG-PET at initial staging that are not confirmed by biopsy or other conventional imaging studies at staging repeat standard imaging at 3- to 6-month follow-up.  Patients with an abnormality that is considered highly suspicious for a metastasis or when biopsy proof of that metastasis is obtained receive treatment at the discretion of the treating physician.  A total of 250 patients (60 with rhabdomyosarcoma) will be recruited.  Patients up to 21 years of age are eligible.  This is a multicenter study; centers have not yet been specified. 

Ecteinascidin 743 in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors. This Phase II study is not yet open for patient recruitment.  The purpose of the trial is to study the effectiveness of ecteinascidin 743 in treating young patients who have recurrent or refractory soft tissue sarcoma (including rhabdomyosarcoma) or Ewing's family of tumors.  Patients are stratified according to disease.  Patients receive ecteinascidin 743 IV over 3 hours on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.  A total of 30-60 patients (10-20 per stratum) will be accrued.  Patients up to 21 years of age are eligible.  This is a multicenter study; centers have not yet been specified.

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