Calcitriol Plus Paclitaxel in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

• Determine the toxic effects and maximum tolerated dose of calcitriol when combined with paclitaxel in patients with advanced solid tumors.
• Determine the effect of administration of calcitriol on the pharmacokinetics of paclitaxel in these patients.
• Determine the effect of administration of paclitaxel on the pharmacokinetics of calcitriol in these patients.

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

During course 1, patients receive oral calcitriol daily on days 1-3 of weeks 1-6 and paclitaxel IV over 1 hour on day 1 of week 1 and day 3 of weeks 2-6. During course 2 and subsequent courses, patients receive oral calcitriol daily on days 1-3 and paclitaxel IV over 1 hour on day 3 of weeks 1-6. Treatment continues every 8 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of calcitriol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose giving an estimated probability of dose-limiting toxicity of no more than 0.30.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven advanced cancer not curable by standard therapies
• Brain metastases allowed following definitive radiotherapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 4 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• Calcium no greater than 10.5 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception for at least 1 week before, during, and for at least 2 weeks after study
• No active infection or serious concurrent condition
• No symptomatic peripheral neuropathy greater than grade 1

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 weeks since prior regional or systemic biologic therapy

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea)

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy

Surgery:

• Not specified