RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Calcitriol may help solid tumor cells develop into normal cells. Combining calcitriol with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of calcitriol combined with carboplatin in treating patients who have advanced solid tumors.

Condition	Treatment or Intervention	Phase
Brain Tumor Genetic Condition Solid Tumor	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: differentiation therapy  Drug: calcitriol  Drug: carboplatin	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated doses of calcitriol and carboplatin, when given in combination, in patients with advanced solid tumors. II. Determine the toxic effects of this regimen in these patients. III. Determine the effect of calcitriol on the pharmacokinetics of carboplatin in these patients. IV. Correlate the pharmacokinetics of carboplatin with the myelosuppression following this regimen in these patients. V. Determine the safety and efficacy of this regimen in patients with malignant glioma.

PROTOCOL OUTLINE: This is a dose-escalation study. Patients are stratified according to disease (brain tumor vs other solid tumor) and accrued in parallel. Patients are assigned to one of two treatment groups. Group 1: Patients receive carboplatin IV over 20-30 minutes on day 1 and calcitriol subcutaneously (SC) or orally daily on days 2-4 for the first course only. For subsequent courses, patients receive calcitriol SC or orally daily on days 1-3 and carboplatin IV over 20-30 minutes on day 3. Group 2: Patients receive calcitriol SC or orally daily on days 1-3 and carboplatin IV over 20-30 minutes on day 3 for the first, third, and subsequent courses. For the second course only, patients receive carboplatin IV over 20-30 minutes on day 1 and calcitriol SC or orally daily on days 2-4. In both groups, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Sequential dose escalation of calcitriol is followed by sequential dose escalation of carboplatin. Cohorts of 3-6 patients receive escalating doses of calcitriol and then carboplatin until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 18-50 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed advanced solid tumor that is not curable by standard therapy, including glioma and other brain tumors
• Brain metastases allowed following definitive radiotherapy

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since prior biologic therapy (regional or systemic)
• Chemotherapy: At least 4 weeks since prior chemotherapy
• Endocrine therapy: No concurrent glucocorticoids as antiemetics; Concurrent exogenous glucocorticoids allowed for treatment of gliomas or other brain tumors
• Radiotherapy: See Disease Characteristics; At least 4 weeks since prior radiotherapy
• Surgery: Not specified
• Other: Dietary calcium intake of no more than 200-250 mg/day beginning 48 hours before each course and continuing for 7 days; No concurrent dairy products, green leafy vegetables, molasses, baking powder, fortified cereals, and dry peas and beans

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 8 weeks
• 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 1.5 mg/dL OR Creatinine clearance at least 60 mL/min AND Creatinine no greater than 2.0 mg/dL; Calcium no greater than 10.5 mg/dL
• Cardiovascular: No unstable angina; No symptomatic coronary artery disease
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use 2 forms of barrier contraception AND 1 form of hormonal contraception for at least 1 week before, during, and for at least 2 weeks after study; No active infection; No other concurrent serious condition

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:  CDR0000068374; PCI-97-004; NCI-G00-1885; PCI-IRB-970532
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00008086
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08