Paricalcitol and Gemcitabine in Treating Patients With Advanced Cancer

Roswell Park Comprehensive Cancer Center

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: paricalcitol; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00217477

CDR0000441212

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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34 participants in 1 patient group

Paricalcitol IV in combination with Gemcitabine IV

Experimental group

Description:

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.

Treatment:

Drug: paricalcitol

Drug: gemcitabine hydrochloride