Paricalcitol and Gemcitabine in Treating Patients With Advanced Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: paricalcitol

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Abbott
• Investigators: Principal Investigator: Renuka Iyer, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: September 20, 2005
• First Submitted That Met QC Criteria: September 20, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): December 9, 2014
• Last Update Submitted That Met QC Criteria: December 8, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: CDR0000441212