Paricalcitol and Gemcitabine in Treating Patients With Advanced Cancer
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Unspecified Adult Solid Tumor, Protocol Specific |
Drug: gemcitabine hydrochloride Drug: paricalcitol |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- 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 ] [ Designated as safety issue: Yes ]
- To assess toxicity. [ Time Frame: 8 week intervals ] [ Designated as safety issue: Yes ]
- To determine the effects of paricalcitol on the pharmacokinetics of gemcitabine. [ Time Frame: Days 1 & 8, cycle 1 ] [ Designated as safety issue: Yes ]
- To determine the effects of pariclcitol on cytidine deaminase in PBM [ Time Frame: Days 1 & 8, cycle 1 ] [ Designated as safety issue: No ]
- To determine the effects of paricalcitol on dFdCTP in PBM [ Time Frame: Days 1 & 8, cycle 1 ] [ Designated as safety issue: No ]
- To determine the pharmacokinetics of paricalcitol when given with gemcitabine [ Time Frame: Day 7, cycle 1 ] [ Designated as safety issue: No ]
- To describe clinical outcome for response and survival [ Time Frame: 8 week intervals ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 44 |
| Study Start Date: | August 2004 |
| Estimated Primary Completion Date: | April 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Paricalcitol IV in combination with Gemcitabine IV
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
Given IV
Drug: paricalcitol
Given IV
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, New York | |
| Roswell Park Cancer Institute | |
| Buffalo, New York, United States, 14263-0001 | |
| Principal Investigator: | Renuka Iyer, MD | Roswell Park Cancer Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | Roswell Park Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00217477 History of Changes |
| Other Study ID Numbers: | CDR0000441212 |
| Study First Received: | September 20, 2005 |
| Last Updated: | December 11, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Roswell Park Cancer Institute:
|
unspecified adult solid tumor, protocol specific |
Additional relevant MeSH terms:
|
Gemcitabine Ergocalciferols Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents |
Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Sensitizing Agents Bone Density Conservation Agents Vitamins Micronutrients Growth Substances |
ClinicalTrials.gov processed this record on June 18, 2013