Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors

Neuroblastoma Clinical Trial

Official title:

An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed by Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003203
• Other study ID #: A9971
• Secondary ID: COG-A9971CCG-997
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: August 22, 2013
• Start date: March 1998
• Est. completion date: March 2012

Study information

• Verified date: August 2013
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and vincristine, work in 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 carboplatin and vincristine with radiation therapy followed by adjuvant chemotherapy may kill more tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy followed adjuvant chemotherapy in treating young patients who have newly diagnosed high-risk CNS embryonal tumors.

Description:

OBJECTIVES:

• Determine the feasible dose and duration of carboplatin combined with craniospinal and local radiotherapy and adjuvant chemotherapy in children with newly diagnosed, high-risk CNS embryonal tumors (Phase I completed as of 11-25-03).

• Determine the feasibility of administering cyclophosphamide and vincristine with or without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these patients.

• Determine the overall and individual toxicity rates of this regimen in these patients.

• Determine the complete response rate in patients treated with this regimen.

• Obtain preliminary estimates of event-free survival of patients treated with this regimen.

• Determine the prognostic significance of enhancing tumor after completion of radiotherapy on event-free survival of these patients.

OUTLINE: This is a pilot, dose-escalation study of carboplatin. (Phase I completed as of 11-25-03.)

Within 31 days of definitive surgery, all patients receive vincristine IV weekly for 6 weeks and carboplatin IV over 15-20 minutes (after completion of vincristine infusion) 5 days a week for 6 weeks. Patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5 days a week for 6 weeks.

Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 3 of 12 patients experience dose-limiting toxicity. (Phase I completed as of 11-25-03.)

At 6 weeks after completion of radiotherapy, patients are assigned to arm II for adjuvant/maintenance chemotherapy. (Arm I closed to accrual as of 11-25-03.)

• Arm I (closed to accrual as of 11-25-03): Patients receive cyclophosphamide IV over 1 hour on days 0 and 1, vincristine IV on days 0 and 7, and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 2 and continuing for at least 10 days until blood counts recover.

• Arm II: Patients receive cyclophosphamide IV over 1 hour on days 1 and 2, vincristine IV on days 0 and 7, cisplatin IV over 6 hours on day 0, and G-CSF IV or SC beginning on day 3 and continuing for at least 10 days until blood counts recover.

In both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses.

Patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: March 2012
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven high-risk CNS embryonal tumors, including:

• Primitive neuroectodermal tumors

• Atypical teratoid/rhabdoid tumor

• Medulloblastoma

• Desmoplastic medulloblastoma

• Ependymoblastoma

• Medullomyoblastoma

• Spongioblastoma

• Spongioblastoma polare

• Primitive polar spongioblastoma

• Neuroepitheliomatous neoplasms

• Medulloepithelioma

• Neuroblastoma

• Pineoblastoma

• No bone marrow involvement or bone metastases

• No M4 disease

• M3 disease must have evidence of tumor on spinal MRI

PATIENT CHARACTERISTICS:

Age:

• 3 to 21 at diagnosis

Performance status:

• Not specified

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3

• Platelet count at least 100,000/mm^3 (transfusion independent)

• Hemoglobin at least 10.0 g/dL (packed red blood cell transfusions allowed)

Hepatic:

• Bilirubin less than 1.5 mg/dL

• SGOT/SGPT less than 2.5 times normal

Renal:

• Creatinine less than 1.5 times upper limit of normal OR

• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Prior definitive surgery allowed

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Neoplasms
• Nervous System Neoplasms
• Neuroblastoma

Intervention

Biological:
• filgrastim
Given IV

Drug:
• carboplatin
Given IV
• cisplatin
Given IV
• cyclophosphamide
Given IV
• vincristine sulfate
Given IV

Procedure:
• adjuvant therapy

Radiation:
• radiation therapy
1.8 Gy/fx x 20fx=36Gy Craniospinal XRT*

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	IWK Grace Health Centre	Halifax	Nova Scotia
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Children's Hospital of Denver	Denver	Colorado
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (2)

Jakacki R, Burger P, Zhou T, et al.: Outcome for metastatic (M+) medulloblastoma (MB) treated with carboplatin during craniospinal radiotherapy (CSRT) followed by cyclophosphamide (CPM) and vincristine (VCR): preliminary results of COG 99701. [Abstract] J

Jakacki RI, Burger PC, Zhou T, Holmes EJ, Kocak M, Onar A, Goldwein J, Mehta M, Packer RJ, Tarbell N, Fitz C, Vezina G, Hilden J, Pollack IF. Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival	Minimum time to disease progression or recurrence, time to death for any reason, or time to occurrence of a second malignant neoplasm (SMN).	Length of study	Yes
Secondary	Survival	Time to death from any cause	Length of study	Yes