Etoposide Plus Radiation Therapy Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed Advanced Medulloblastoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003573
First received: November 1, 1999
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

RATIONALE: 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 radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of etoposide plus radiation therapy followed by combination chemotherapy in treating children with newly diagnosed advanced medulloblastoma.


Condition Intervention Phase
Brain Tumors
Central Nervous System Tumors
Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Feasibility Study of Oral Etoposide Given Concurrently With Radiotherapy Followed With Dose Intensive Adjuvant Chemotherapy for Children With Newly Diagnosed High Stage Medulloblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Assess the efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy followed with dose intensive adjuvant chemotherapy in children with newly diagnosed high stage medulloblastoma [ Time Frame: End of course 1 (week 10) ] [ Designated as safety issue: Yes ]
    It is possible that unacceptably high levels of toxicity may arise. For this reason, there is a 3-stage stopping rule designed to allow the Study Coordinator to stop this study early if it appears that the true proportion of eligible patients who suffer unacceptable levels of toxicity exceeds 10%.


Enrollment: 53
Study Start Date: November 1998
Study Completion Date: March 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment 1, Etoposide, 50mg/m2/day

Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiation therapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7).

Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Biological: filgrastim
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen®
  • NSC #614629
Drug: cisplatin
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • Platinol
  • NSC #119875
Drug: cyclophosphamide
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271
  • IND #7089
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
  • IND #9197
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
  • IND #7161
Radiation: radiation therapy
Experimental: Treatment 2, Etoposide, 35mg/m2/day

Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiation therapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7).

Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Biological: filgrastim
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen®
  • NSC #614629
Drug: cisplatin
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • Platinol
  • NSC #119875
Drug: cyclophosphamide
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271
  • IND #7089
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
  • IND #9197
Drug: vincristine sulfate
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
  • IND #7161
Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Assess the response rate and toxicity of oral etoposide and radiotherapy in children with newly diagnosed high stage medulloblastoma.
  • Compare the response rate and toxicity of these patients to historical control patients registered on POG #9031.
  • Estimate the 2-year event-free survival and overall survival of these patients.
  • Evaluate the toxicity of dose intensive chemotherapy with oral etoposide, cisplatin, cyclophosphamide, and vincristine following craniospinal irradiation in these patients.

OUTLINE: Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiotherapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7).

Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and annually thereafter.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within about 2 years.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically diagnosed advanced (high grade) childhood medulloblastoma
  • Residual disease of at least 1.5 cm2 in size on MRI or CT scan OR
  • Evidence of CNS or extraneural metastases

PATIENT CHARACTERISTICS:

Age:

  • 3 to 21

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • SGPT less than 5 times normal
  • Bilirubin less than 1.5 mg/dL

Renal:

  • Creatinine less than 1.7 mg/dL OR
  • Creatinine clearance greater than 70 mL/min

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Prior corticosteroids allowed

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003573

  Show 106 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Albert Moghrabi, MD Hopital Sainte Justine
  More Information

Additional Information:
No publications provided by Children's Oncology Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003573     History of Changes
Other Study ID Numbers: 9631, POG-9631, CDR0000066640
Study First Received: November 1, 1999
Last Updated: July 24, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood medulloblastoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Medulloblastoma
Neoplasms
Nervous System Neoplasms
Glioma
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Cisplatin
Cyclophosphamide
Etoposide
Etoposide phosphate
Lenograstim
Vincristine
Adjuvants, Immunologic
Alkylating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 21, 2014