Paricalcitol and Gemcitabine in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open Label, Dose Escalation Study of Paricalcitol (Zemplar™) [19-NOR-1 ALPHA, 25-(OH) D] in Combination With Gemcitabine [2', 2' -Difluorodeoxycytidine] in Patients With Advanced Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: paricalcitol


Participation Criteria
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Eligibility Criteria
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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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paricalcitol IV in combination with Gemcitabine IV<br>Patients receive gemcitabine hydrochloride 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 hydrochloride IV over 80 minutes on days 2, 9, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: gemcitabine hydrochloride<br>* Given IV<br>Drug: paricalcitol<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess toxicity. |  | 8 week intervals | 
| To determine the effects of paricalcitol on the pharmacokinetics of gemcitabine. |  | Days 1 & 8, cycle 1 | 
| To determine the effects of pariclcitol on cytidine deaminase in PBM |  | Days 1 & 8, cycle 1 | 
| To determine the effects of paricalcitol on dFdCTP in PBM |  | Days 1 & 8, cycle 1 | 
| To determine the pharmacokinetics of paricalcitol when given with gemcitabine |  | Day 7, cycle 1 | 
| To describe clinical outcome for response and survival |  | 8 week intervals | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific