Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief summary
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
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.
Interventions
DRUGgemcitabine hydrochloride
Given IV
DRUGparicalcitol
Given IV
Sponsors
Abbott
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 assess toxicity. | 8 week intervals |
| 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 |
| To determine the effects of paricalcitol on dFdCTP in PBM | Days 1 & 8, cycle 1 |
Countries
United States
Outcome results
None listed