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 temozolomide in treating patients who have advanced solid tumors that have spread to the brain.

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

Further Study Details: 

OBJECTIVES: I. Assess the response rate of patients with cerebral metastases who have failed or refused standard therapy when treated with temozolomide. II. Assess the safety and tolerability of this drug in these patients. III. Determine the quality of life of patients treated with this drug. IV. Determine the response rate of systemic disease outside the central nervous system in patients treated with this drug.

PROTOCOL OUTLINE: Patients receive oral temozolomide daily for 6 weeks. Treatment repeats every 10 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Quality of life is assessed on day 1 of each 10-week course. Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 18-48 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced solid malignancy with imaging evidence of progressive brain metastases; Failed or refused surgery, whole brain radiotherapy, and/or stereotactic radiosurgery; No lymphoma; Systemic disease allowed (if uncontrolled, must be less life-threatening than brain metastases)
• Bidimensionally measurable brain disease by MRI; Previously treated lesions must show progression and be measurable
• No known carcinomatous meningitis

--Prior/Concurrent Therapy--

• Biologic therapy: At least 2 weeks since prior biologic therapy or immunotherapy and recovered; No concurrent growth factors administered for the purpose of continuing temozolomide; No concurrent epoetin alfa
• Chemotherapy: Prior adjuvant chemotherapy allowed; Prior chemotherapy for metastatic disease allowed; At least 4 weeks since prior chemotherapy except vincristine (6 weeks for nitrosoureas or mitomycin) and recovered
• Endocrine therapy: Prior and concurrent steroids allowed if neurologically stable or improving; Concurrent hormonal therapy allowed for stable breast cancer
• Radiotherapy: See Disease Characteristics; At least 2 weeks since prior radiotherapy or interstitial brachytherapy (4 weeks for brain radiotherapy) and recovered; No concurrent radiotherapy
• Surgery: See Disease Characteristics; At least 1 week since prior surgery and recovered
• Other: At least 4 weeks since prior systemic therapy; No other concurrent investigational agents

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• 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
• 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 3 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; No known HIV infection; No other malignancy within the past 2 years except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin; No other serious medical condition; No acute infection treated with IV antibiotics; No frequent vomiting or other medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction)

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States

Study chairs or principal investigators

Judith M. Ford,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068485; UCLA-0004059; NCI-G01-1919; SPRI-UCLA-0004059
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012116
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08