Clinical trial NCT00047177: Oxaliplatin in Treating Children With Recurrent or Refractory Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor
Official title: A Phase II Study of Oxaliplatin in Children With Recurrent or Refractory Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumors and Atypical Teratoid Rhabdoid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood ependymoma
childhood atypical teratoid/rhabdoid tumor
Lead sponsor: Pediatric Brain Tumor Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 43
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of oxaliplatin in treating children who have recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal or atypical teratoid rhabdoid tumor.

Detailed description: OBJECTIVES:

* Estimate the objective response rate to oxaliplatin in pediatric patients with recurrent or refractory medulloblastoma at first progression.
* Estimate the objective response rate to oxaliplatin in pediatric patients with recurrent or refractory medulloblastoma at second or later relapse.
* Estimate the objective response rate to oxaliplatin in pediatric patients with recurrent or refractory supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor.
* Describe the pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (medulloblastoma \[measurable disease at first relapse vs positive cerebrospinal fluid or linear leptomeningeal disease vs measurable disease at second or later progression\] vs supratentorial primitive neuroectodermal tumor vs atypical teratoid rhabdoid tumor).

Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study within 1.5-2.8 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed medulloblastoma, supratentorial primitive neuroectodermal tumor (including pineoblastomas and ependymoblastomas), or atypical teratoid rhabdoid tumor

  * Recurrent or refractory disease
* Measurable disease by radiography
* Patients with positive cerebrospinal fluid cytology or linear leptomeningeal disease are eligible

PATIENT CHARACTERISTICS:

Age

* 21 and under

Performance status

* Karnofsky 50-100% OR
* Lansky 50-100%

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 1,000/mm\^3
* Platelet count at least 100,000/mm\^3 (transfusion independent)
* Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)

Hepatic

* Bilirubin no greater than 1.5 times normal
* ALT less than 2.5 times normal

Renal

* Creatinine no greater than 1.5 times normal OR
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular

* Shortening fraction at least 27% by echocardiogram OR
* Ejection fraction at least 50% by MUGA

Pulmonary

* No dyspnea at rest
* No exercise intolerance
* Pulse oximetry greater than 94%

Other

* No uncontrolled infection
* No active graft-versus-host disease
* No uncontrolled seizure disorders

  * Seizure disorders well controlled with anticonvulsants allowed
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* At least 2 weeks since prior growth factors
* At least 6 months since prior allogeneic stem cell transplantation
* No concurrent colony-stimulating factors during the first course of study
* No concurrent immunomodulating agents

Chemotherapy

* At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosoureas) and recovered
* No other concurrent anticancer chemotherapy

Endocrine therapy

* If concurrent corticosteroids necessary for intracranial pressure, must be on stable or decreasing dose for at least 1 week prior to study
* No other concurrent corticosteroids

Radiotherapy

* At least 2 weeks since prior local palliative radiotherapy (small port) to symptomatic metastatic sites
* At least 3 months since prior craniospinal radiotherapy
* No concurrent palliative radiotherapy
* Recovered from prior radiotherapy

Surgery

* Not specified

Other

* No other concurrent anticancer or experimental drugs

Primary outcomes:
measure: Objective response rate to oxaliplatin in recurrent or progressive medulloblastoma at first progression
measure: Objective response rate to oxaliplatin in recurrent or refractory medulloblastoma at second or later relapse
Secondary outcomes:
measure: Objective response rate to oxaliplatin in recurrent or progressive supratentorial PNETs or atypical teratoid rhabdoid tumor (ATRT)
measure: Pharmacokinetics of oxaliplatin in the serum and CSF
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Cancer Center
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Maryam Fouladi, MD
role: STUDY_CHAIR
References:
citation: Fouladi M, Blaney SM, Poussaint TY, Freeman BB 3rd, McLendon R, Fuller C, Adesina AM, Hancock ML, Danks MK, Stewart C, Boyett JM, Gajjar A. Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study. Cancer. 2006 Nov 1;107(9):2291-7. doi: 10.1002/cncr.22241.