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Gemcitabine +/- Imatinib Mesylate, Patients w/Previously Treated Metastatic Breast Cancer

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
gemcitabine hydrochloride
imatinib mesylate
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring recurrent breast cancer, stage IV breast cancer, male breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Locally advanced or metastatic disease Disease progression after at least 1 prior chemotherapy regimen for metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease (prior neoadjuvant or adjuvant treatment will not be included in determining the number of prior chemotherapy regimens) Measurable disease No known symptomatic or untreated brain metastases or carcinomatous meningitis Previously treated and clinically stable brain metastases allowed provided patient has been off steroids for > 7 days Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or 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 contraception during and for 3 months after completion of study therapy Able to swallow oral medication No coexisting medical condition that would preclude study compliance No uncontrolled illness, including any of the following: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia requiring therapy Myocardial infarction within the past 6 months Active infection No New York Heart Association class III-IV cardiac disease No history of allergic reaction attributed to compounds of similar chemical or biologic composition to gemcitabine hydrochloride and/or imatinib mesylate No other primary malignancies within the past 5 years except for carcinoma in situ of the cervix or nonmelanoma skin cancer No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known HIV infection PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy More than 2 weeks since prior surgery At least 2 weeks since prior hormonal therapy At least 2 weeks since prior trastuzumab (Herceptin®) At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy More than 28 days since prior investigational agents At least 3 weeks since prior radiotherapy Must have evidence of ≥ 1 measurable target lesion outside the irradiated fields OR radiologically confirmed disease progression within the irradiated fields after completion of radiotherapy No prior imatinib mesylate for metastatic disease No prior gemcitabine hydrochloride for metastatic disease More than 6 months since prior adjuvant gemcitabine hydrochloride No other concurrent investigational or commercial agents No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin® or Coumadine®) Concurrent heparin or low-molecular weight heparin (e.g., Lovenox®) for therapeutic anticoagulation allowed Concurrent prophylactic warfarin therapy (e.g., mini-dose Coumadin® ≤ 1 mg daily) to maintain catheter patency allowed No concurrent routine chronic systemic corticosteroids No concurrent medications that would preclude study compliance

Sites / Locations

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • University of Maryland Greenebaum Cancer Center
  • Cooper Hospital/University Medical Center
  • Rutgers Cancer Institute of New Jersey at Hamilton
  • Mountainside Hospital
  • Jersey Shore Cancer Center at Jersey Shore University Medical Center
  • Rutgers Cancer Institute of New Jersey
  • Saint Peter's University Hospital
  • NJ Medical School

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I (Gemcitabine Hydrochloride)

Arm II (Gemcitabine Hydrochloride + Imatinib)

Arm Description

Patients receive gemcitabine hydrochloride IV on days 3 and 10.

Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12.

Outcomes

Primary Outcome Measures

Time to Progression
Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided).

Secondary Outcome Measures

Response Rate (Complete and Partial Response)
Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response(OR) defined as OR=CR + PR
Overall Survival

Full Information

First Posted
May 8, 2006
Last Updated
March 27, 2023
Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Novartis Pharmaceuticals, Rutgers Cancer Institute of New Jersey
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1. Study Identification

Unique Protocol Identification Number
NCT00323063
Brief Title
Gemcitabine +/- Imatinib Mesylate, Patients w/Previously Treated Metastatic Breast Cancer
Official Title
Randomized Phase II Trial of Gemcitabine and Imatinib Mesylate Versus Gemcitabine Alone in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
May 1, 2006 (Actual)
Primary Completion Date
April 15, 2011 (Actual)
Study Completion Date
June 20, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Novartis Pharmaceuticals, Rutgers Cancer Institute of New Jersey

4. Oversight

Data Monitoring Committee
No

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 to gemcitabine alone in treating patients with previously treated locally advanced or metastatic breast cancer.
Detailed Description
OBJECTIVES: Primary Compare time to progression in patients with previously treated locally advanced or metastatic breast cancer treated with gemcitabine hydrochloride with vs without imatinib mesylate. Secondary Compare the efficacy of these regimens in these patients. Compare the overall survival of patients treated with these regimens. Compare the safety and tolerability of these regimens in these patients. OUTLINE: This is a multicenter, open-label, randomized study. Patients 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 once daily on days 1-5 and 8-12. In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 80 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
Breast Cancer
Keywords
recurrent breast cancer, stage IV breast cancer, male breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (Gemcitabine Hydrochloride)
Arm Type
Active Comparator
Arm Description
Patients receive gemcitabine hydrochloride IV on days 3 and 10.
Arm Title
Arm II (Gemcitabine Hydrochloride + Imatinib)
Arm Type
Experimental
Arm Description
Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12.
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Time to Progression
Description
Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided).
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Response Rate (Complete and Partial Response)
Description
Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response(OR) defined as OR=CR + PR
Time Frame
5 years
Title
Overall Survival
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Locally advanced or metastatic disease Disease progression after at least 1 prior chemotherapy regimen for metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease (prior neoadjuvant or adjuvant treatment will not be included in determining the number of prior chemotherapy regimens) Measurable disease No known symptomatic or untreated brain metastases or carcinomatous meningitis Previously treated and clinically stable brain metastases allowed provided patient has been off steroids for > 7 days Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or 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 contraception during and for 3 months after completion of study therapy Able to swallow oral medication No coexisting medical condition that would preclude study compliance No uncontrolled illness, including any of the following: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia requiring therapy Myocardial infarction within the past 6 months Active infection No New York Heart Association class III-IV cardiac disease No history of allergic reaction attributed to compounds of similar chemical or biologic composition to gemcitabine hydrochloride and/or imatinib mesylate No other primary malignancies within the past 5 years except for carcinoma in situ of the cervix or nonmelanoma skin cancer No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No known HIV infection PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy More than 2 weeks since prior surgery At least 2 weeks since prior hormonal therapy At least 2 weeks since prior trastuzumab (Herceptin®) At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) At least 3 weeks since prior anti-vascular endothelial growth factor therapy More than 28 days since prior investigational agents At least 3 weeks since prior radiotherapy Must have evidence of ≥ 1 measurable target lesion outside the irradiated fields OR radiologically confirmed disease progression within the irradiated fields after completion of radiotherapy No prior imatinib mesylate for metastatic disease No prior gemcitabine hydrochloride for metastatic disease More than 6 months since prior adjuvant gemcitabine hydrochloride No other concurrent investigational or commercial agents No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin® or Coumadine®) Concurrent heparin or low-molecular weight heparin (e.g., Lovenox®) for therapeutic anticoagulation allowed Concurrent prophylactic warfarin therapy (e.g., mini-dose Coumadin® ≤ 1 mg daily) to maintain catheter patency allowed No concurrent routine chronic systemic corticosteroids No concurrent medications that would preclude study compliance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah R. Toppmeyer, MD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-3013
Country
United States
Facility Name
University of Maryland Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Cooper Hospital/University Medical Center
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey at Hamilton
City
Hamilton
State/Province
New Jersey
ZIP/Postal Code
08690
Country
United States
Facility Name
Mountainside Hospital
City
Montclair
State/Province
New Jersey
ZIP/Postal Code
07042
Country
United States
Facility Name
Jersey Shore Cancer Center at Jersey Shore University Medical Center
City
Neptune
State/Province
New Jersey
ZIP/Postal Code
07754
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Saint Peter's University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
NJ Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States

12. IPD Sharing Statement

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Gemcitabine +/- Imatinib Mesylate, Patients w/Previously Treated Metastatic Breast Cancer

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