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.
- Determine the maximum tolerated doses of calcitriol and carboplatin, when given in
combination, in patients with advanced solid tumors.
- Determine the toxic effects of this regimen in these patients.
- Determine the effect of calcitriol on the pharmacokinetics of carboplatin in these
- Correlate the pharmacokinetics of carboplatin with the myelosuppression following this
regimen in these patients.
- Determine the safety and efficacy of this regimen in patients with malignant glioma.
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
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
PROJECTED ACCRUAL: Approximately 18-50 patients will be accrued for this study.
- Histologically confirmed advanced solid tumor that is not curable by standard
therapy, including glioma and other brain tumors
- Brain metastases allowed following definitive radiotherapy
- 18 and over
- ECOG 0-2
- At least 8 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 mg/dL
- SGOT no greater than 4 times normal
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
- Creatinine no greater than 2.0 mg/dL
- Calcium no greater than 10.5 mg/dL
- No unstable angina
- No symptomatic coronary artery disease
- 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
- No active infection
- No other concurrent serious condition
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior biologic therapy (regional or systemic)
- At least 4 weeks since prior chemotherapy
- No concurrent glucocorticoids as antiemetics
- Concurrent exogenous glucocorticoids allowed for treatment of gliomas or other brain
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy
- Not specified
- 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