Clinical trial NCT00005637: Combination Chemotherapy Following Radiation Therapy in Treating Patients With Malignant Glioma
Official title: A Phase I Study of Extended Low Dose Temozolomide (SCH 52365, Temodar (R)) and Carmustine (BCNU) in the Treatment of Malignant Gliomas After Radiation Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma
adult anaplastic ependymoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_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. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy following radiation therapy in treating patients who have malignant glioma.

Detailed description: OBJECTIVES:

* Determine the safety and efficacy of extended low-dose temozolomide when combined with carmustine after radiotherapy in patients with malignant glioma.
* Determine the maximum tolerated dose of this combination in this patient population.
* Determine time to progression as measured from baseline gadolinium-enhanced magnetic resonance imaging in patients treated with this regimen.

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

Patients receive oral temozolomide once daily on days 1-28 and carmustine IV over 1-3 hours beginning within 72 hours after starting temozolomide. Courses repeat every 8 weeks for up to 1 year in the absence of unacceptable toxicity or disease progression.

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 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant glioma

  * Glioblastoma
  * Gliosarcoma
  * High-grade glioma
  * Anaplastic astrocytoma
  * Anaplastic mixed oligoastrocytoma
  * Anaplastic oligodendroglioma
  * Anaplastic ependymoma
* Must have completed radiotherapy

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* More than 3 months

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic:

* Bilirubin less than 1.5 times upper limit of normal (ULN)
* SGOT/SGPT less than 3 times ULN
* Alkaline phosphatase less than 2 times ULN

Renal:

* BUN less than 1.5 times ULN
* Creatinine less than 1.5 times ULN

Pulmonary:

* Pulmonary function test with diffusion greater than 50 OR
* Clearance by the pulmonary service

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No AIDS-related illness
* No nonmalignant systemic disease that would preclude study
* No acute infection requiring IV antibiotics
* No psychiatric condition that would preclude study compliance
* No frequent vomiting or medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction)
* No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior immunotherapy
* No prior biologic therapy

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics
* At least 2 weeks since prior radiotherapy

Surgery:

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jeffrey J. Raizer, MD
role: STUDY_CHAIR
References: