Combination Chemotherapy Followed by Second-Look Surgery and Radiation Therapy in Treating Children With Nonmetastatic Medulloblastoma or Primitive Neuroectodermal Tumor

Children's Oncology Group

Status and phase: Completed; Phase 3

Conditions: Untreated Childhood Medulloblastoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Treatments: Drug: vincristine sulfate; Radiation: 3-dimensional conformal radiation therapy; Procedure: therapeutic conventional surgery; Drug: etoposide; Drug: cyclophosphamide; Drug: cisplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00006461

POG-P9934 (Other Identifier)

P9934

U10CA098543 (U.S. NIH Grant/Contract)

CDR0000068269 (Other Identifier)

COG-P9934 (Other Identifier)

NCI-2012-02362 (Registry Identifier)

Details and patient eligibility

About

This phase III trial is studying how well combination chemotherapy followed by second-look surgery and radiation therapy works in treating children with nonmetastatic medulloblastoma or primitive neuroectodermal tumor. Drugs used in chemotherapy use 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 more than one drug and combining chemotherapy with surgery and radiation therapy may kill more tumor cells.

Full description

PRIMARY OBJECTIVES:

I. To determine if the proposed treatment for children >= 8.0 months and < 3 years of age at registration with non-metastatic (M0) medulloblastoma is more effective than the combined treatments given to children of the same age and extent of disease on POG 9233, as measured by event-free survival (EFS) rates.

SECONDARY OBJECTIVES:

I. To assess the feasibility and safety of the planned use of second look surgery and focal conformal radiation therapy following chemotherapy. II. To determine the acute and chronic toxicities associated with the above treatment regimens.

III. To describe the neuropsychological and neuroendocrine effects of this systemic chemotherapy, surgery, and local, conformal radiation. IV. To determine the feasibility and validity of a centralized telephone interview based data collection method for neuropsychological evaluations. V. To determine the incidence of atypical teratoid/rhabdoid tumor (AT/RT) in children enrolled on this study.

OUTLINE: This is a multicenter study.

Patients receive induction chemotherapy consisting of vincristine IV on days 1, 8, and 15; cisplatin IV over 6 hours on day 1; cyclophosphamide IV over 30 minutes on day 2; and oral etoposide daily on days 2-22. Treatment repeats every 28 days for a total of 4 courses. After completion of induction chemotherapy, patients with residual disease undergo a second resection. Within 4 weeks after completion of induction chemotherapy or second resection, patients receive focal conformal radiotherapy daily, 5 days a week, for 6 weeks. Four weeks after completion of radiotherapy, patients receive alternating treatments of maintenance chemotherapy. Patients receive vincristine IV on days 1, 8, and 15 and cyclophosphamide IV over 30 minutes on day 1 of courses 1, 3, 5, and 7 and oral etoposide daily on days 1-21 of courses 2, 4, 6, and 8. Treatment continues every 28 days for 8 courses. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Enrollment: 82 patients

Sex: All

Ages: Under 3 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed primary medulloblastoma or posterior fossa primitive neuroectodermal tumor

  • Prior definitive tumor resection within 6 weeks of study

• No evidence of metastases

• Hemoglobin at least 10 g/dL

• Absolute neutrophil count at least 1,500/mm3

• Platelet count at least 100,000/mm3

• AST less than 2.5 times normal

• Bilirubin less than 1.5 mg/dL

• Creatinine less than 1.2 mg/dL

• Creatinine clearance greater than 70 mL/min

• No prior chemotherapy

• No prior radiotherapy

• See Disease Characteristics

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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82 participants in 1 patient group

Chemotherapy, surgery, radiation therapy

Other group

Description:

Patients receive induction chemotherapy consisting of vincristine sulfate IV on days 1, 8, and 15; cisplatin IV over 6 hours on day 1; cyclophosphamide IV over 30 minutes on day 2; and oral etoposide daily on days 2-22. Treatment repeats every 28 days for a total of 4 courses. After completion of induction chemotherapy, patients with residual disease undergo a therapeutic conventional surgery (second resection). Within 4 weeks after completion of induction chemotherapy or second resection, patients receive 3-dimensional conformal radiation therapy daily, 5 days a week, for 6 weeks. Four weeks after completion of 3-dimensional conformal radiation therapy, patients receive alternating treatments of maintenance chemotherapy. Patients receive vincristine sulfate IV on days 1, 8, and 15 and cyclophosphamide IV over 30 minutes on day 1 of courses 1, 3, 5, and 7 and oral etoposide daily on days 1-21 of courses 2, 4, 6, and 8. Treatment continues every 28 days for 8 courses.

Treatment:

Drug: cisplatin

Drug: cyclophosphamide

Drug: etoposide

Radiation: 3-dimensional conformal radiation therapy

Drug: vincristine sulfate

Procedure: therapeutic conventional surgery