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

PURPOSE: Phase I/II trial to study the effectiveness of temozolomide and vinorelbine in treating patients who have recurrent brain metastases.

Condition	Treatment or Intervention	Phase
brain metastases	Drug: temozolomide  Drug: vinorelbine  Procedure: chemotherapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of vinorelbine when administered in combination with temozolomide in patients with recurrent brain metastases (phase I accrual completed).
• Determine the safety and feasibility of this treatment regimen in these patients.
• Determine the efficacy of this treatment regimen, in terms of objective radiographic response and overall and progression-free survival, in these patients.

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

Patients receive vinorelbine IV over 5-10 minutes on days 1 and 8 and oral temozolomide once daily on days 1-7 and 15-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 20-35 patients will be treated at that dose level.

Patients are followed every 3-4 months.

PROJECTED ACCRUAL: A minimum of 3 patients will be accrued for the phase I portion of this study and 20-35 patients will be accrued for the phase II portion of this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor with metastases to the brain
• Evaluable disease in brain by MRI or CT scan

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 8 weeks

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 and SGPT no greater than 3 times ULN
• Alkaline phosphatase no greater than 2 times ULN

Renal:

• Creatinine less than 1.5 times ULN
• BUN less than 1.5 times ULN

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No AIDS-related illness
• No nonmalignant systemic disease
• No psychiatric condition that would preclude study
• No acute infection requiring IV antibiotics
• No frequent vomiting or medical condition that would preclude oral medication intake (i.e., partial bowel obstruction)

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior biologic therapy or immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No prior temozolomide, dacarbazine, or vinorelbine
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior external beam radiotherapy
• At least 8 weeks since prior stereotactic radiosurgery
• Concurrent focal radiotherapy for progressive bony disease allowed if brain metastases are stable or responding

Surgery:

• At least 2 weeks since prior brain biopsy, craniotomy, or other surgery

Other:

• Recovered from all prior therapy

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Lauren E. Abrey, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000069035; MSKCC-01088A; NCI-G01-2025; NCT00026494
Record last reviewed:  September 2004
Last Updated:  February 4, 2005
Record first received:  November 9, 2001
ClinicalTrials.gov Identifier:  NCT00026494
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08