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
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
4 weeks
Safety Issue:
Yes
Principal Investigator
Renuka Iyer, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000441212
NCT ID:
NCT00217477
Start Date:
August 2004
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
