Paricalcitol and Gemcitabine in Treating Patients With Advanced Cancer

Roswell Park Cancer Institute34 enrolled

Overview

RATIONALE: Paricalcitol may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving paricalcitol together with gemcitabine may be an effective treatment for cancer. PURPOSE: This phase I trial is studying the side effects and best dose of paricalcitol when given together with gemcitabine in treating patients with advanced cancer.

OBJECTIVES: Primary * Determine the maximum tolerated dose (MTD) of paricalcitol when given with gemcitabine in patients with advanced malignancy. Secondary * Determine safety and toxicity of this regimen in these patients. * Determine the pharmacokinetics of these regimens in these patients. * Determine the clinical outcome (overall survival and best overall response) of patients treated with this regimen. OUTLINE: This is a dose-escalation, open-label study. Patients receive gemcitabine IV over 80 minutes on days 1, 8, and 15 and paricalcitol IV over 15 minutes on days 7 and 14 in course 1. Beginning in course 2, patients receive paricalcitol IV over 15 minutes on days 1, 8, and 15 and gemcitabine IV over 80 minutes on days 2, 9, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of paricalcitol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A minimum of 6 patients are treated at the MTD. After completion of study treatment, patients are followed for survival. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Interventions

gemcitabine hydrochlorideDRUG

Given IV

paricalcitolDRUG

Given IV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Diagnosis of advanced malignancy * Metastatic or unresectable disease * Standard curative or palliative measures do not exist or are no longer effective * No known brain metastases * Patients with previously treated brain metastases are eligible provided they have recovered from prior treatment PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * At least 3 months Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 mg/dL * AST and ALT ≤ 3.0 times upper limit of normal Renal * Creatinine ≤ 2.0 mg/dL * Corrected calcium ≤ 10.5 mg/dL * Prior single confirmed urolithiasis allowed provided patient is free of stone formation for ≥ 5 years * No calculi in the urinary tract on kidney ultrasound biopsy or other imaging studies Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs * No other uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * More than 4 weeks since prior chemotherapy and recovered Endocrine therapy * Not specified Radiotherapy * More than 4 weeks since prior radiotherapy and recovered Surgery * Not specified Other * Curative therapy for a condition associated with the risk of renal stones (e.g., hyperparathyroidism, bladder dysfunction, or obstructive uropathy) allowed provided patients have been free of stone formation for ≥ 5 years * No concurrent digoxin * No other concurrent investigational agents

Locations (1)

Roswell Park Cancer Institute

Buffalo, New York, United States

Outcomes

Primary Outcomes

To determine the maximum tolerated dose (MTD) of i. v. pancalcitol given weekly, in combination with fixed dose rate infusion of i. v.gemcitabine given weekly in patients with advanced malignancies.

Time frame: 4 weeks

Secondary Outcomes

To assess toxicity.

Time frame: 8 week intervals

To determine the effects of paricalcitol on the pharmacokinetics of gemcitabine.

Time frame: Days 1 & 8, cycle 1

To determine the effects of pariclcitol on cytidine deaminase in PBM

Time frame: Days 1 & 8, cycle 1

To determine the effects of paricalcitol on dFdCTP in PBM

Time frame: Days 1 & 8, cycle 1

To determine the pharmacokinetics of paricalcitol when given with gemcitabine

Time frame: Day 7, cycle 1

To describe clinical outcome for response and survival

Time frame: 8 week intervals

Data from ClinicalTrials.gov

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