HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
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|ClinicalTrials.gov Identifier: NCT02875314|
Recruitment Status : Recruiting
First Posted : August 23, 2016
Last Update Posted : March 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Medulloblastoma Central Nervous System Embryonal Tumors||Drug: Induction Drug: Single Cycle Intensive Chemotherapy Drug: Tandem 3 Cycle Intensive Chemotherapy||Phase 4|
Due to the inferior response and event-free survival data of Regimens D and D2 on "Head Start III" for all children with supratentorial embryonal tumors, in comparison with the published data from "Head Start II" with Regimen A2 for metastatic patients, all such patients will receive the "Head Start II" Induction Regimen A2, on "Head Start 4", for either three or five cycles, depending upon whether or not they achieve complete remission by the end of Induction cycle #3. They will then undergo randomization to either single cycle or three tandem cycles of Consolidation marrow-ablative chemotherapy with AuHPCR.
Because of the unsatisfactory event-free survival for young children with non-desmoplastic/extensive nodular medulloblastoma (predominantly non-Shh and non-Wnt medulloblastoma subgroups) on Regimens D and D2 of "Head Start III", all these patients will receive the "Head Start II" Induction Regimen A2 on ""Head Start 4"", for either three or five cycles, depending upon whether or not they achieve complete remission by the end of Induction cycle #3. They will then undergo randomization to either single cycle or three tandem cycles of Consolidation marrow-ablative chemotherapy with AuHPCR.
Because of the excellent event-free and overall survival for young children with good risk medullo-blastoma (Shh or Wnt subgroups) treated with up-front "Head Start" chemotherapy strategies, such patients will undergo risk-tailored reduction of duration of Induction therapy from five cycles to three cycles of the "Head Start II" Induction Regimen A2 on "Head Start 4" for patients achieving a complete response to 3 cycles, followed, provided they are also without evidence of residual tumor following recovery from Induction cycle #3. They will NOT then undergo randomization, but will follow with a single cycle of Consolidation marrow-ablative chemotherapy as in "Head Start" studies.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||250 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation With Randomization to Either Single Cycle or to Three Tandem Cycles of Marrow-Ablative Chemotherapy With Autologous Hematopoietic Progenitor Cell Rescue|
|Study Start Date :||September 2015|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2020|
The 5 chemotherapy drugs used in the Induction part of treatment are vincristine, cisplatin, cyclophosphamide, etoposide and high-dose methotrexate.
Three medications are also given to help reduce the side effects of the chemotherapy drugs. Filgrastim will be given through a vein or through a tiny needle into the tissue just under the skin to help blood counts recover after the chemotherapy. Mesna will be given through a vein with cyclophosphamide to help prevent bleeding in the bladder. Leucovorin will be given through a vein after the methotrexate to protect the body from the side effects of the methotrexate.
vincristine, cisplatin, cyclophosphamide, etoposide, high-dose methotrexate
Other Name: vincristine, cisplatin, cyclophosphamide, etoposide, high-dose methotrexate
Experimental: Single Cycle Intensive Chemotherapy
The three drugs to be used in this research study are thiotepa, etoposide and carboplatin. These drugs will be given over 6 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter.
Carboplatin is given by vein over 4 hours. Thiotepa is given by vein over 3 hours. Etoposide is given by vein over 3 hours. The schedule for these drugs is as follows:
Day -8: Carboplatin Day -7: Carboplatin Day -6: Carboplatin Day -5: Thiotepa, Etoposide Day -4: Thiotepa, Etoposide Day -3: Thiotepa, Etoposide Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells
Drug: Single Cycle Intensive Chemotherapy
Carboplatin, thiotepa, etoposide
Other Name: Carboplatin, thiotepa, etoposide
Experimental: Tandem 3 Cycle Intensive Chemotherapy
The 2 drugs to be used in this treatment are thiotepa and carboplatin. These drugs will be given over 2 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter.
Day -4: Thiotepa, Carboplatin Day -3: Thiotepa, Carboplatin Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells.
Following recovery from the first cycle of this chemotherapy, about 28 days following the Day 0 reinfusion of blood cells, the same cycle will be repeated again. A total of 3 cycles of this therapy will be administered, over the course of 12 weeks.
Drug: Tandem 3 Cycle Intensive Chemotherapy
Other Name: Carboplatin, thiotepa
- Compare tandem consolidation vs. single cycle consolidation A [ Time Frame: 5 years ]Dose-intensive tandem Consolidation will be compared with single cycle consolidation via randomization. The randomized consolidations will provide an event-free survival (EFS) analysis after completing "Head Start 4" Induction.
- Compare tandem consolidation vs. single cycle consolidation B [ Time Frame: 5 years ]Dose-intensive tandem Consolidation will be compared with single cycle consolidation via randomization. The randomized consolidations will provide an overall survival (OS) analysis after completing "Head Start 4" Induction.
- Induction Cycle Reduction [ Time Frame: 5 years ]Induction chemotherapy cycles will be reduced in number from five to three for molecularly high-risk medulloblastoma (non-Shh/non-Wnt) and CNS embryonal tumors who achieve a complete response (CR) after three cycles of Induction therapy results in equivalent 3-year EFS. Outcome will be analyzed irrespective of Consolidation assignment (Primary Aim) and compared to historical controls.
- Uniform Treatment Regimen [ Time Frame: 5 years ]Assess the rate of response of sequential dose-intensive and dose-compressed Induction chemotherapy followed by marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHPCR) for children with medulloblastoma and other CNS embryonal tumors enrolled on the "Head Start 4" study utilizing a uniform treatment regimen.
- Therapy-Related Hearing Loss Evaluation A [ Time Frame: 5 years ]The prevalence and severity of therapy-related hearing loss as a function of cumulative dosing of cisplatin (three versus five cycles during Induction) will be evaluated. Distortion-Product Oto-acoustic Emissions (DPOAE) will be used as an early predictor of hearing loss to identify at-risk patients.
- Therapy-Related Hearing Loss Evaluation B [ Time Frame: 5 years ]The prevalence and severity of therapy-related hearing loss as a function of AuHPCR (one versus three tandem transplants in Consolidation) will be evaluated. Distortion-Product Oto-acoustic Emissions (DPOAE) will be used as an early predictor of hearing loss to identify at-risk patients.
- Neuropsychological effects will be evaluated using age based tests and questionnaires. [ Time Frame: 5 years ]The long-term neuropsychological effects will be evaluated.
- Endocrine studies will be conducted using Serum-free T4, TSH, Cortisol, IGF and IGFBP3 laboratory tests. [ Time Frame: 5 years ]The long-term endocrine functions effect will be evaluated.
- Physical growth will be evaluated by collecting patient's height, weight and BSA. [ Time Frame: 5 years ]The long-term physical growth effect will be evaluated.
- The development of second neoplasms will be monitored. [ Time Frame: 5 years ]The long-term development of second neoplasms will be evaluated.
- Neuropathology Biorepository and Clinical Database [ Time Frame: 5 years ]The study will establish a "Head Start 4" repository of clinical, radiographic and biologic specimens, including nucleic acids derived from these specimens, for future genomic, biologic and pharmacologic research.
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): NCT02875314
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