Calcitriol Plus Carboplatin in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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 patients. 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 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.

Official Title
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A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in Advanced Solid Tumors

Conditions
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Brain and Central Nervous System Tumors, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: calcitriol
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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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 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/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 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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: calcitriol|nan|
|Drug: carboplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult medulloblastoma, recurrent adult brain tumor, adult brain stem glioma, adult craniopharyngioma, adult meningioma, adult glioblastoma, unspecified adult solid tumor, protocol specific, adult anaplastic astrocytoma, adult myxopapillary ependymoma, adult anaplastic ependymoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult central nervous system germ cell tumor, adult pilocytic astrocytoma, adult subependymoma, adult ependymoblastoma, adult pineocytoma, adult pineoblastoma, adult meningeal hemangiopericytoma, adult choroid plexus tumor, adult grade III meningioma, adult oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma