Clinical trial NCT00003203: Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Tumors
Central Nervous System Tumors
Neuroblastoma
Keywords: untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma
localized unresectable neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-19
Enrollment: 168
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Event Free Survival
timeFrame: Length of study
Secondary outcomes:
measure: Survival
timeFrame: Length of study
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Denver
country: United States
facility: Children's Hospital of Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: IWK Grace Health Centre
state: Nova Scotia
Study officials:
affiliation: University of Pittsburgh
name: Regina Jakacki, MD
role: STUDY_CHAIR
References:
citation: 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 Children's Oncology Group Phase I/II study. J Clin Oncol. 2012 Jul 20;30(21):2648-53. doi: 10.1200/JCO.2011.40.2792. Epub 2012 Jun 4.
citation: 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 Clin Oncol 25 (Suppl 18): A-2017, 2007.