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

Systemic Chemotherapy, Second Look Surgery and Conformal Radiation Therapy Limited to the Posterior Fossa and Primary Site for Children >/= to 8 Months and <3 Years With Non-metastatic Medulloblastoma: A Children&Apos;s Oncology Group Phase III Study

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.

Study Overview

• Status: Completed
• Conditions: Untreated Childhood Medulloblastoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
• Intervention / Treatment: Drug: cyclophosphamide; Drug: vincristine sulfate; Drug: cisplatin; Procedure: therapeutic conventional surgery; Radiation: 3-dimensional conformal radiation therapy; Drug: etoposide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Chemotherapy, surgery, radiation therapy; 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.

Drug: cyclophosphamide; Given IV; Other Names: Cytoxan; Endoxan; CPM; CTX; Endoxana; Drug: vincristine sulfate; Given IV; Other Names: VCR; leurocristine sulfate; Vincasar PFS; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Procedure: therapeutic conventional surgery; Undergo surgery; Radiation: 3-dimensional conformal radiation therapy; Undergo 3-dimensional conformal radiation therapy; Other Names: 3D-CRT; 3D conformal radiation therapy; Drug: etoposide; Given PO; Other Names: EPEG; VP-16; VP-16-213

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival rate	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Acute and chronic toxicities associated with the treatment regimens	Up to 9 years
Neuropsychological and neuroendocrine effects of this systemic chemotherapy, surgery, and local, conformal radiation	Up to 9 years
Feasibility and validity of a centralized telephone interview based data collection method for neuropsychological evaluations	Up to 9 years
Incidence of atypical teratoid and/or rhabdoid tumor	Up to 9 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David Ashley, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: November 6, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): August 9, 2013
• Last Update Submitted That Met QC Criteria: August 7, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Etoposide; Etoposide phosphate; Cisplatin; Vincristine
• Other Study ID Numbers: P9934; U10CA098543 (U.S. NIH Grant/Contract); NCI-2012-02362 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000068269 (Other Identifier: Clinical Trials.gov); POG-P9934 (Other Identifier: Pediatric Oncology Group); COG-P9934 (Other Identifier: Children's Oncology Group)