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

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
Information provided by:
Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier:
NCT00323791
First received: May 8, 2006
Last updated: December 10, 2009
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Drug: gemcitabine hydrochloride
Drug: imatinib mesylate
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase II Trial of Gemzar (Gemcitabine) and Gleevec (Imatinib Mesylate) in Patients With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Stable disease [ Designated as safety issue: No ]
  • Objective response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Expression of c-KIT and platelet-derived growth factor receptor-alpha protein expression [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: April 2006
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00323791

Locations
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
University of Medicine and Dentistry New Jersey
Investigators
Principal Investigator: Mark Stein, MD Rutgers Cancer Institute of New Jersey
  More Information

No publications provided

Responsible Party: Mark Stein, MD, UMDNJ/CINJ
ClinicalTrials.gov Identifier: NCT00323791     History of Changes
Other Study ID Numbers: CDR0000539400, P30CA072720, CINJ-080507, CINJ-5633, CINJ-NJ3805
Study First Received: May 8, 2006
Last Updated: December 10, 2009
Health Authority: United States: Federal Government

Keywords provided by Rutgers, The State University of New Jersey:
recurrent renal cell cancer
clear cell renal cell carcinoma
papillary renal cell carcinoma
stage IV renal cell cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Gemcitabine
Imatinib
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
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014