Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors
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|ClinicalTrials.gov Identifier: NCT00003203|
Recruitment Status : Completed
First Posted : May 19, 2003
Last Update Posted : August 23, 2013
RATIONALE: Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining carboplatin and vincristine with radiation therapy followed by adjuvant chemotherapy may kill more tumor cells.
PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy followed adjuvant chemotherapy in treating young patients who have newly diagnosed high-risk CNS embryonal tumors.
|Condition or disease||Intervention/treatment||Phase|
|Brain Tumors Central Nervous System Tumors Neuroblastoma||Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: vincristine sulfate Procedure: adjuvant therapy Radiation: radiation therapy||Phase 2|
- Determine the feasible dose and duration of carboplatin combined with craniospinal and local radiotherapy and adjuvant chemotherapy in children with newly diagnosed, high-risk CNS embryonal tumors (Phase I completed as of 11-25-03).
- Determine the feasibility of administering cyclophosphamide and vincristine with or without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these patients.
- Determine the overall and individual toxicity rates of this regimen in these patients.
- Determine the complete response rate in patients treated with this regimen.
- Obtain preliminary estimates of event-free survival of patients treated with this regimen.
- Determine the prognostic significance of enhancing tumor after completion of radiotherapy on event-free survival of these patients.
OUTLINE: This is a pilot, dose-escalation study of carboplatin. (Phase I completed as of 11-25-03.)
Within 31 days of definitive surgery, all patients receive vincristine IV weekly for 6 weeks and carboplatin IV over 15-20 minutes (after completion of vincristine infusion) 5 days a week for 6 weeks. Patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5 days a week for 6 weeks.
Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 3 of 12 patients experience dose-limiting toxicity. (Phase I completed as of 11-25-03.)
At 6 weeks after completion of radiotherapy, patients are assigned to arm II for adjuvant/maintenance chemotherapy. (Arm I closed to accrual as of 11-25-03.)
- Arm I (closed to accrual as of 11-25-03): Patients receive cyclophosphamide IV over 1 hour on days 0 and 1, vincristine IV on days 0 and 7, and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 2 and continuing for at least 10 days until blood counts recover.
- Arm II: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2, vincristine IV on days 0 and 7, cisplatin IV over 6 hours on day 0, and G-CSF IV or SC beginning on day 3 and continuing for at least 10 days until blood counts recover.
In both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses.
Patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||168 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed by Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors|
|Study Start Date :||March 1998|
|Primary Completion Date :||October 2007|
|Study Completion Date :||March 2012|
Experimental: Newly diagnosed cerebral PNET with histologic verification
Begin therapy within 31 days of surgery. Radiation therapy will be given in standard fractions along with filgrastim. The craniospinal axis will be treated first. Patients will receive carboplatin at 35 mg/m2/day IV over 15-20 minutes Monday through Friday, 1-4 hours prior to radiation for 6 weeks (total of 30 doses). Vincristine sulfate 1.5 mg/m2 IV will be given weekly x 6. Following radiation, patients will receive Maintenance chemotherapy. Patients enrolled prior to Amendment #5 will receive six cycles of cyclophosphamide and vincristine (Regimen A). Patients enrolled after Amendment #5 will receive six cycles of cyclophosphamide, vincristine sulfate and cisplatin (Regimen B).
Other Names:Drug: carboplatin
Other Names:Drug: cisplatin
Other Names:Drug: cyclophosphamide
Other Names:Drug: vincristine sulfate
Other Names:Procedure: adjuvant therapy Radiation: radiation therapy
1.8 Gy/fx x 20fx=36Gy Craniospinal XRT*
Other Name: radiotherapy
- Event Free Survival [ Time Frame: Length of study ]Minimum time to disease progression or recurrence, time to death for any reason, or time to occurrence of a second malignant neoplasm (SMN).
- Survival [ Time Frame: Length of study ]Time to death from any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003203
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|Study Chair:||Regina Jakacki, MD||Children's Hospital of Pittsburgh of UPMC|