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Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma
NCT02306161
Sponsor: National Cancer Institute (NCI)
Principal Investigator: Steven DuBois, Children’s Oncology Group and Dana-Farber Cancer Institute, Boston.
Study locations: Over 300 U.S. cancer centers
Study summary: This randomized phase 3 trial examines whether the monoclonal antibody ganitumab plus combination chemotherapy (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide) improves event-free survival for patients with newly-diagnosed, metastatic Ewing sarcoma. Secondary outcomes include overall survival rate and comparative evaluations of toxicity.
Patients are randomized to induction and consolidation therapy with vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]) or to the same regimen plus ganitumab. Between weeks 13-18 of the trial, patients undergo surgery and/or radiation therapy for local control. Patients with lung metastases undergo definitive stereotactic body radiation therapy or external beam radiation therapy over 5 days.
Study inclusion summary: Patients up to 50 years old are eligible to participate in this trial if they have newly-diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site. Submission of pre-treatment serum, tumor tissue and whole blood is required. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery. Creatinine clearance or radioisotope glomerular filtration rate (GFR) must be at least 70 mL/min/1.73 m2 or greater. Total bilirubin must be less than 1.5 times the upper limit of normal, alanine aminotransferase must be less than 3 times the upper limit of normal, blood sugar must be normal, and heart ejection fraction must exceed 50%.
Induction therapy: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. Patients in the control group receive induction therapy and placebo and patients in the treatment group receive induction therapy and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.
Consolidation therapy: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. In addition to this standard consolidation therapy, pPatients in the active treatment group receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.
Maintenance therapy: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.
Follow up: After completion of study treatment, patients are followed for 10 years.
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT02567435
Sponsor: National Cancer Institute (NCI)
Principal Investigator: Abha Gupta, Children’s Oncology Group, The Hospital for Sick Children and Princess Margaret Cancer Centre.
Study locations: 293 cancer centers in the U.S. and Canada
Study summary: This randomized phase 3 trial compares standard combination chemotherapy with and without temsirolimus for patients with rhabdomyosarcoma that has an intermediate chance of recurrence after treatment. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.
Study inclusion summary: Patients up to age 40 with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study. Lansky performance status score must be at least 50 for patients age 16 years and under; Karnofsky performance status score must be 50 or greater for patients over age 16. Peripheral absolute neutrophil count must be at least 750/uL and platelet count at least 75,000/uL. Creatinine clearance or radioisotope glomerular filtration rate must be at least 70 mL/min/1.73 m2. Total bilirubin must be no more than 1.5 times the upper limit of normal for patient age.
Treatment regimen: Patients are randomized to one of three study arms. One group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. The second group receives the same regimen plus temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. The third group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients in all three groups also undergo radiation therapy beginning at week 13 for 6 weeks. Treatment continues in all three groups in the absence of disease progression or unacceptable toxicity.
Outcome Measures: The primary outcome measure is event-free survival (EFS) measured from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm, or death as a first event. The secondary outcome measure is overall survival measured from study enrollment to death from any cause, assessed up to 10 years. TSJ
Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma
NCT02306161
Sponsor: National Cancer Institute (NCI)
Principal Investigator: Steven DuBois, Children’s Oncology Group and Dana-Farber Cancer Institute, Boston.
Study locations: Over 300 U.S. cancer centers
Study summary: This randomized phase 3 trial examines whether the monoclonal antibody ganitumab plus combination chemotherapy (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide) improves event-free survival for patients with newly-diagnosed, metastatic Ewing sarcoma. Secondary outcomes include overall survival rate and comparative evaluations of toxicity.
Patients are randomized to induction and consolidation therapy with vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]) or to the same regimen plus ganitumab. Between weeks 13-18 of the trial, patients undergo surgery and/or radiation therapy for local control. Patients with lung metastases undergo definitive stereotactic body radiation therapy or external beam radiation therapy over 5 days.
Study inclusion summary: Patients up to 50 years old are eligible to participate in this trial if they have newly-diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site. Submission of pre-treatment serum, tumor tissue and whole blood is required. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery. Creatinine clearance or radioisotope glomerular filtration rate (GFR) must be at least 70 mL/min/1.73 m2 or greater. Total bilirubin must be less than 1.5 times the upper limit of normal, alanine aminotransferase must be less than 3 times the upper limit of normal, blood sugar must be normal, and heart ejection fraction must exceed 50%.
Induction therapy: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. Patients in the control group receive induction therapy and placebo and patients in the treatment group receive induction therapy and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.
Consolidation therapy: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. In addition to this standard consolidation therapy, pPatients in the active treatment group receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.
Maintenance therapy: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.
Follow up: After completion of study treatment, patients are followed for 10 years.
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT02567435
Sponsor: National Cancer Institute (NCI)
Principal Investigator: Abha Gupta, Children’s Oncology Group, The Hospital for Sick Children and Princess Margaret Cancer Centre.
Study locations: 293 cancer centers in the U.S. and Canada
Study summary: This randomized phase 3 trial compares standard combination chemotherapy with and without temsirolimus for patients with rhabdomyosarcoma that has an intermediate chance of recurrence after treatment. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.
Study inclusion summary: Patients up to age 40 with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study. Lansky performance status score must be at least 50 for patients age 16 years and under; Karnofsky performance status score must be 50 or greater for patients over age 16. Peripheral absolute neutrophil count must be at least 750/uL and platelet count at least 75,000/uL. Creatinine clearance or radioisotope glomerular filtration rate must be at least 70 mL/min/1.73 m2. Total bilirubin must be no more than 1.5 times the upper limit of normal for patient age.
Treatment regimen: Patients are randomized to one of three study arms. One group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. The second group receives the same regimen plus temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. The third group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients in all three groups also undergo radiation therapy beginning at week 13 for 6 weeks. Treatment continues in all three groups in the absence of disease progression or unacceptable toxicity.
Outcome Measures: The primary outcome measure is event-free survival (EFS) measured from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm, or death as a first event. The secondary outcome measure is overall survival measured from study enrollment to death from any cause, assessed up to 10 years. TSJ
Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma
NCT02306161
Sponsor: National Cancer Institute (NCI)
Principal Investigator: Steven DuBois, Children’s Oncology Group and Dana-Farber Cancer Institute, Boston.
Study locations: Over 300 U.S. cancer centers
Study summary: This randomized phase 3 trial examines whether the monoclonal antibody ganitumab plus combination chemotherapy (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide) improves event-free survival for patients with newly-diagnosed, metastatic Ewing sarcoma. Secondary outcomes include overall survival rate and comparative evaluations of toxicity.
Patients are randomized to induction and consolidation therapy with vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]) or to the same regimen plus ganitumab. Between weeks 13-18 of the trial, patients undergo surgery and/or radiation therapy for local control. Patients with lung metastases undergo definitive stereotactic body radiation therapy or external beam radiation therapy over 5 days.
Study inclusion summary: Patients up to 50 years old are eligible to participate in this trial if they have newly-diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site. Submission of pre-treatment serum, tumor tissue and whole blood is required. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery. Creatinine clearance or radioisotope glomerular filtration rate (GFR) must be at least 70 mL/min/1.73 m2 or greater. Total bilirubin must be less than 1.5 times the upper limit of normal, alanine aminotransferase must be less than 3 times the upper limit of normal, blood sugar must be normal, and heart ejection fraction must exceed 50%.
Induction therapy: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. Patients in the control group receive induction therapy and placebo and patients in the treatment group receive induction therapy and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.
Consolidation therapy: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. In addition to this standard consolidation therapy, pPatients in the active treatment group receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.
Maintenance therapy: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.
Follow up: After completion of study treatment, patients are followed for 10 years.
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT02567435
Sponsor: National Cancer Institute (NCI)
Principal Investigator: Abha Gupta, Children’s Oncology Group, The Hospital for Sick Children and Princess Margaret Cancer Centre.
Study locations: 293 cancer centers in the U.S. and Canada
Study summary: This randomized phase 3 trial compares standard combination chemotherapy with and without temsirolimus for patients with rhabdomyosarcoma that has an intermediate chance of recurrence after treatment. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.
Study inclusion summary: Patients up to age 40 with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study. Lansky performance status score must be at least 50 for patients age 16 years and under; Karnofsky performance status score must be 50 or greater for patients over age 16. Peripheral absolute neutrophil count must be at least 750/uL and platelet count at least 75,000/uL. Creatinine clearance or radioisotope glomerular filtration rate must be at least 70 mL/min/1.73 m2. Total bilirubin must be no more than 1.5 times the upper limit of normal for patient age.
Treatment regimen: Patients are randomized to one of three study arms. One group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. The second group receives the same regimen plus temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. The third group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients in all three groups also undergo radiation therapy beginning at week 13 for 6 weeks. Treatment continues in all three groups in the absence of disease progression or unacceptable toxicity.
Outcome Measures: The primary outcome measure is event-free survival (EFS) measured from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm, or death as a first event. The secondary outcome measure is overall survival measured from study enrollment to death from any cause, assessed up to 10 years. TSJ