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Gemcitabine With or Without Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Kidney Cancer

Primary Purpose

Kidney Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
gemcitabine hydrochloride
imatinib mesylate
gene expression analysis
protein expression analysis
immunohistochemistry staining method
laboratory biomarker analysis
Sponsored by
University of Medicine and Dentistry of New Jersey
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring recurrent renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma, stage IV renal cell cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed renal cell carcinoma Metastatic disease OR unresectable primary tumor No known curative therapy exists Documented progressive renal cell carcinoma as defined by RECIST criteria within the past 6 months Measurable disease with ≥ 1 unidimensionally measurable lesion No known symptomatic brain metastasis or untreated brain metastases or carcinomatous meningitis Treated brain metastasis allowed provided the following criteria are met: Clinically stable More than 7 days since prior steroids PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment Must be able to swallow oral medication No coexisting medical condition that would preclude study compliance No history of allergic reaction to compounds of similar chemical or biological composition to gemcitabine hydrochloride and/or imatinib mesylate No uncontrolled illness that would preclude study participation No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia requiring therapy No myocardial infarction within the past 6 months No active infection No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer No New York Heart Association class III-IV congestive heart failure No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known HIV positivity No significant history of noncompliance to medical regimens PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy No more than 3 prior treatment regimens, including any of the following: No more than 1 prior cytotoxic therapy Immunotherapy regimens comprising interferon and/or aldesleukin Therapy with molecular targets Any combination of the above treatments to a maximum of 3 total therapies No prior gemcitabine hydrochloride for metastatic disease No prior imatinib mesylate for metastatic disease More than 2 weeks since prior major surgery At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy At least 3 weeks since prior radiotherapy Must have evidence of ≥ 1 measurable target lesion outside the radiation fields OR radiologically confirmed disease progression within the radiation fields after completion of radiotherapy At least 28 days since prior and no other concurrent investigational or commercial agents, unless disease is rapidly progressing No concurrent therapeutic warfarin Concurrent low molecular weight heparin or heparin allowed for therapeutic anticoagulation Concurrent prophylactic warfarin therapy ≤ 1 mg daily to maintain catheter patency allowed No concurrent filgrastim (G-CSF) for prevention of neutropenia No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery No concurrent routine use (i.e., daily or every other day) of systemic corticosteroid therapy (in supraphysiologic doses) No concurrent medication that would preclude study compliance

Sites / Locations

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Outcomes

Primary Outcome Measures

Stable disease
Objective response

Secondary Outcome Measures

Median survival
Progression-free survival
Response rate
Expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression

Full Information

First Posted
May 8, 2006
Last Updated
December 10, 2009
Sponsor
University of Medicine and Dentistry of New Jersey
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00323791
Brief Title
Gemcitabine With or Without Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Kidney Cancer
Official Title
A Phase II Trial of Gemzar (Gemcitabine) and Gleevec (Imatinib Mesylate) in Patients With Metastatic Renal Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2009
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
April 2006 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Medicine and Dentistry of New Jersey
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This randomized phase II trial is studying gemcitabine and imatinib mesylate to see how well they work compared with gemcitabine alone in treating patients with metastatic or unresectable kidney cancer.
Detailed Description
OBJECTIVES: Primary Compare stable disease and objective response in patients with metastatic or unresectable renal cell carcinoma treated with gemcitabine hydrochloride with or without imatinib mesylate. Secondary Evaluate the median survival, progression-free survival, and response rate in patients treated with gemcitabine hydrochloride and imatinib mesylate. Determine the qualitative and quantitative toxic effects of this regimen in these patients. Determine the expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression in both tumor cells and associated endothelial cells using immunohistochemistry staining of paraffin-embedded tissue. OUTLINE: This is a randomized, multicenter study. Patients are stratified by histology (clear cell vs nonclear cell) and prior therapy (immunotherapy/chemotherapy vs targeted agents). Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate on days 1-5 and 8-12. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving partial or complete response after 2 courses of treatment continue treatment with gemcitabine hydrochloride and imatinib mesylate in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses of treatment are randomized to 1 of 2 treatment arms. Arm I: Patients receive gemcitabine hydrochloride IV on days 3 and 10. Arm II: Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate on days 1-5 and 8-12. In both arms, treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Available archived tumor tissue samples are obtained for immunohistochemical analysis to quantify the expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
recurrent renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma, stage IV renal cell cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Intervention Type
Genetic
Intervention Name(s)
gene expression analysis
Intervention Type
Genetic
Intervention Name(s)
protein expression analysis
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Primary Outcome Measure Information:
Title
Stable disease
Title
Objective response
Secondary Outcome Measure Information:
Title
Median survival
Title
Progression-free survival
Title
Response rate
Title
Expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed renal cell carcinoma Metastatic disease OR unresectable primary tumor No known curative therapy exists Documented progressive renal cell carcinoma as defined by RECIST criteria within the past 6 months Measurable disease with ≥ 1 unidimensionally measurable lesion No known symptomatic brain metastasis or untreated brain metastases or carcinomatous meningitis Treated brain metastasis allowed provided the following criteria are met: Clinically stable More than 7 days since prior steroids PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment Must be able to swallow oral medication No coexisting medical condition that would preclude study compliance No history of allergic reaction to compounds of similar chemical or biological composition to gemcitabine hydrochloride and/or imatinib mesylate No uncontrolled illness that would preclude study participation No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia requiring therapy No myocardial infarction within the past 6 months No active infection No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer No New York Heart Association class III-IV congestive heart failure No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known HIV positivity No significant history of noncompliance to medical regimens PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy No more than 3 prior treatment regimens, including any of the following: No more than 1 prior cytotoxic therapy Immunotherapy regimens comprising interferon and/or aldesleukin Therapy with molecular targets Any combination of the above treatments to a maximum of 3 total therapies No prior gemcitabine hydrochloride for metastatic disease No prior imatinib mesylate for metastatic disease More than 2 weeks since prior major surgery At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy At least 3 weeks since prior radiotherapy Must have evidence of ≥ 1 measurable target lesion outside the radiation fields OR radiologically confirmed disease progression within the radiation fields after completion of radiotherapy At least 28 days since prior and no other concurrent investigational or commercial agents, unless disease is rapidly progressing No concurrent therapeutic warfarin Concurrent low molecular weight heparin or heparin allowed for therapeutic anticoagulation Concurrent prophylactic warfarin therapy ≤ 1 mg daily to maintain catheter patency allowed No concurrent filgrastim (G-CSF) for prevention of neutropenia No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery No concurrent routine use (i.e., daily or every other day) of systemic corticosteroid therapy (in supraphysiologic doses) No concurrent medication that would preclude study compliance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Stein, MD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

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Gemcitabine With or Without Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Kidney Cancer

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