A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in 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.
Primary Purpose: Treatment
Ramesh K. Ramanathan, MD
University of Pittsburgh
United States: Federal Government
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|