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

Randomized Phase II Trial of Gemcitabine and Imatinib Mesylate Versus Gemcitabine Alone in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: imatinib mesylate

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital/University Medical Center
    • Hamilton, New Jersey, United States, 08690
      • Rutgers Cancer Institute of New Jersey at Hamilton
    • Montclair, New Jersey, United States, 07042
      • Mountainside Hospital
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore Cancer Center at Jersey Shore University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Saint Peter's University Hospital
    • Newark, New Jersey, United States, 07103
      • NJ Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (Gemcitabine Hydrochloride); Patients receive gemcitabine hydrochloride IV on days 3 and 10.	Drug: gemcitabine hydrochloride; Given IV
Experimental: Arm II (Gemcitabine Hydrochloride + Imatinib); Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12.	Drug: gemcitabine hydrochloride; Given IV; Drug: imatinib mesylate; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		5 years
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	5 years

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Novartis Pharmaceuticals; Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Deborah R. Toppmeyer, MD, Rutgers Cancer Institute of New Jersey

Publications and helpful links

Helpful Links

• Breast cancer - triple negative/cytotoxics/local therapy

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2006
• Primary Completion (Actual): April 15, 2011
• Study Completion (Actual): June 20, 2016

Study Registration Dates

• First Submitted: May 8, 2006
• First Submitted That Met QC Criteria: May 8, 2006
• First Posted (Estimate): May 9, 2006

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; male breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Imatinib Mesylate
• Other Study ID Numbers: 0220060081 (Other Identifier: IRB Number); P30CA072720 (U.S. NIH Grant/Contract); CDR0000539445 (Other Identifier: NIH); NJ1105 (Other Identifier: CINJOG number); NCI-2012-00520 (Other Identifier: NCI); 040504 (Other Identifier: Rutgers Cancer Institute of New Jersey)