Clinical trial NCT00323063: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Novartis Pharmaceuticals
name: Rutgers Cancer Institute of New Jersey
First posted: 2006-05-09
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to Progression
timeFrame: 5 years
Secondary outcomes:
measure: Response Rate (Complete and Partial Response)
timeFrame: 5 years
measure: Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Camden
country: United States
facility: Cooper Hospital/University Medical Center
state: New Jersey
city: Hamilton
country: United States
facility: Rutgers Cancer Institute of New Jersey at Hamilton
state: New Jersey
city: Montclair
country: United States
facility: Mountainside Hospital
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore Cancer Center at Jersey Shore University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: Newark
country: United States
facility: NJ Medical School
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Deborah R. Toppmeyer, MD
role: PRINCIPAL_INVESTIGATOR
References: