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

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.