Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma

NCT ID: NCT00031590

Last Updated: 2019-04-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-04-30
• Study Completion Date: 2011-05-31

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving higher dose radiation to children with newly diagnosed average risk medulloblastoma.

Detailed Description

OBJECTIVES:

• By giving reduced dose craniospinal radiation followed by nine cycles of maintenance chemotherapy comprised of alternating cycles of lomustine, cisplatin, and vincristine alternating with cyclophosphamide and etoposide, we will reduce the late effects of higher dose radiation in children while maintaining the therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy
• To evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multi center study of reduced dose craniospinal radiotherapy and chemotherapy in patients ages 3 - 30 years with newly diagnosed average risk medulloblastoma.

• Induction chemoradiotherapy: Beginning within 28 days after complete surgical resection, patients undergo radiotherapy to the craniospinal axis (1800 centigray (cGy)) followed by conformal radiotherapy to the tumor bed (5400 cGy). Patients receive vincristine weekly for 6 weeks.
• Maintenance chemotherapy: Beginning 4 weeks after the completion of craniospinal radiation therapy, patients receive two 6-week courses of regimen A as outlined below alternating with one 6-week course of regimen B for a total of 9 courses (AABAABAAB).

• Regimen A: Patients receive oral lomustine and cisplatin on day 0 and vincristine on days 0, 7, and 14.
• Regimen B: Patients receive cyclophosphamide on days 0 and 1 and etoposide intravenous (IV) on days 0 and 1, followed by oral etoposide on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter with surveillance neuroimaging using Magnetic Resonance Imaging Scan (MRI scan) and clinical examination.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.

Conditions

Brain Tumors; Central Nervous System Tumors; Medulloblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Treatment

All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide \[IV and oral\]) which will be given in the following order: AABAABAAB (total of 54 weeks).

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only).

Cyclophosphamide

Intervention Type: DRUG

Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Administration of cyclophosphamide will always be preceded by prehydration and Mesna (Regimen B only).

Etoposide

Intervention Type: DRUG

Given at a dose of 150mg/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Given orally at a dose of 50mg/m2 as a single daily dose for 21 days beginning on day 14 of a cycle (Regimen B only).

Lomustine

Intervention Type: DRUG

Given at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only).

Vincristine

Intervention Type: DRUG

Given at a dose of 1.5mg/m2 given by IV infusion once a week for the first six weeks of treatment during radiation therapy. During maintenance therapy, it will be given as an IV push on days 0, 7 and 14 of each 6-week cycle (Regimen A only).

Craniospinal Radiation

Intervention Type: RADIATION

Craniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (vincristine).

Interventions

Cisplatin

Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only).

Intervention Type: DRUG

Cyclophosphamide

Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Administration of cyclophosphamide will always be preceded by prehydration and Mesna (Regimen B only).

Intervention Type: DRUG

Etoposide

Given at a dose of 150mg/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Given orally at a dose of 50mg/m2 as a single daily dose for 21 days beginning on day 14 of a cycle (Regimen B only).

Intervention Type: DRUG

Lomustine

Given at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only).

Intervention Type: DRUG

Vincristine

Given at a dose of 1.5mg/m2 given by IV infusion once a week for the first six weeks of treatment during radiation therapy. During maintenance therapy, it will be given as an IV push on days 0, 7 and 14 of each 6-week cycle (Regimen A only).

Intervention Type: DRUG

Craniospinal Radiation

Craniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (vincristine).

Intervention Type: RADIATION

Other Intervention Names

CDDP; Platinum; Cytoxan; VP-16; CCNU; Oncovin; Radiation

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed medulloblastoma

2. Standard-risk disease

3. No residual tumor greater than 1.5 cm^2 after resection by postoperative MRI

• No tumor in the spinal or cerebral subarachnoid space by MRI
• No tumor in the subarachnoid space by Cerebrospinal fluid (CSF)
• No failure to perform staging studies (spine MRI and CSF cytology) preoperatively or postoperatively

4. Must begin radiotherapy on study within 28 days after surgery

Exclusion Criteria

1. Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed.

2. Pregnant females will not be eligible

3. Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator.

4. Patients with the following will not be eligible:

• > 1.5cm3 residual tumor following resection as indicated by post-operative MRI.
• tumor in spinal or cerebral subarachnoid space either by MRI of brain and spine
• tumor in subarachnoid space by CSF cytology
• failure to perform staging studies (spine MRI, CSF cytology) either pre- or post- operatively

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter C. Phillips, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

Minturn JE, Mochizuki AY, Partap S, Belasco JB, Lange BJ, Li Y, Phillips PC, Gibbs IC, Fisher PG, Fisher MJ, Janss AJ. A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma. Front Oncol. 2021 Sep 2;11:744739. doi: 10.3389/fonc.2021.744739. eCollection 2021.

Reference Type: DERIVED

PMID: 34540703 (View on PubMed)

Other Identifiers

CHP-693

Identifier Type: OTHER

Identifier Source: secondary_id

00-002301

Identifier Type: -

Identifier Source: org_study_id