RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Calcitriol may increase the effectiveness of paclitaxel by making tumor cells more sensitive to the drug. PURPOSE: Phase I trial to study the effectiveness of combining calcitriol with paclitaxel in treating patients who have advanced solid tumors.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Procedure: chemotherapy  Procedure: biological response modifier therapy  Drug: chemosensitization/potentiation  Procedure: differentiation therapy  Drug: calcitriol  Drug: paclitaxel	Phase I

Further Study Details: 

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

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

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

--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

--Patient Characteristics--

Age: 18 and over

Performance status: ECOG 0-2

Life expectancy: Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3

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

Pennsylvania
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States

Study chairs or principal investigators

Ramesh K. Ramanathan,  Study Chair,  University of Pittsburgh Cancer Institute   

Study ID Numbers:  CDR0000068411; PCI-98019; NCI-G00-1901; PCI-IRB-980542
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  February 2, 2001
ClinicalTrials.gov Identifier:  NCT00009802
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08