Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Brain Cancer

Sponsor

NYU Langone Health (Other)

Overall Status

Completed

CT.gov ID

NCT00025558

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining temozolomide, thiotepa, and carboplatin followed by peripheral stem cell transplantation or bone marrow transplantation in treating patients who have brain cancer.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Biological: filgrastim Drug: carboplatin Drug: temozolomide Drug: thiotepa Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of temozolomide in combination with thiotepa and carboplatin followed by autologous peripheral blood stem cell or bone marrow transplantation in patients with recurrent high-grade brain tumors with minimal residual disease or newly-diagnosed malignant glioma with minimal residual disease following irradiation.

OUTLINE: This is a dose-escalation study of temozolomide.

Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 3 consecutive days. After the third dose of G-CSF, patients undergo leukapheresis to collect peripheral blood stem cells (PBSC). Patients who do not have adequate PBSC may undergo bone marrow harvest.

Patients then receive oral temozolomide every 12 hours on days -10 to -6 and thiotepa IV over 3 hours and carboplatin IV over 4 hours on days -5 to -3.

PBSC or bone marrow are reinfused on day 0. Beginning on day 1, patients receive G-CSF SC or IV until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at day 42, at 3 months, every 3 months for 2 years, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Dose Escalation of Temozolomide in Combination With Thiotepa and Carboplatin With Autologous Stem Cell Rescue in Patients With Malignant Brain Tumors With Minimal Residual Disease

Study Start Date :

Oct 1, 2000

Actual Primary Completion Date :

May 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 49 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of one of the following malignant brain tumors:
Anaplastic astrocytoma
Glioblastoma multiforme
Anaplastic oligodendroglioma
Medulloblastoma
High-grade ependymoma
Germ cell tumors
Pineoblastoma
Other primitive neuroectodermal tumors
Recurrent disease or resistant to conventional therapy (e.g., surgery, radiotherapy, or standard chemotherapy)
No prior myeloablative doses of thiotepa OR
Newly diagnosed malignant glioma with minimal residual disease after prior radiotherapy
Minimal residual disease is defined as tumor with maximum diameter of less than 1.5 cm by MRI and no corticosteroid dependency

PATIENT CHARACTERISTICS:

Age:

Over 1 to under 50

Performance status:

Karnofsky 70-100% OR
Lansky 70-100%

Life expectancy:

More than 12 weeks

Hematopoietic:

Absolute neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3
Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

Bilirubin less than 1.5 times upper limit of normal (ULN)
SGOT/SGPT less than 2.5 times ULN
Alkaline phosphatase less than 2.5 times ULN

Renal:

Creatinine less than 1.5 times ULN
Creatinine clearance at least 70 mL/min
BUN less than 1.5 times ULN

Cardiovascular:

Ejection fraction greater than 50% OR
Shortening fraction greater than 27%
No evidence of myocardial ischemia on EKG if over 40 years of age

Other:

HIV negative
No AIDS-related illness
No frequent vomiting or medical condition that would preclude oral medication (e.g., partial bowel obstruction)
No other malignancy within the past 2 years except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 2 weeks since prior biologic therapy or immunotherapy

Chemotherapy:

See Disease Characteristics
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

See Disease Characteristics

Radiotherapy:

See Disease Characteristics
At least 6 weeks since prior radiotherapy and recovered
At least 6 weeks since prior brachytherapy or radiosurgery

Surgery:

See Disease Characteristics
Recovered from prior major surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
2	Columbus Children's Hospital	Columbus	Ohio	United States	43205-2696
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
4	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001