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S0338, Imatinib Mesylate and Capecitabine in Treating Women With Progressive Stage IV Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00087152
First received: July 8, 2004
Last updated: May 12, 2014
Last verified: February 2013
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining imatinib mesylate with capecitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with capecitabine works in treating women with progressive stage IV breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Capecitabine
Drug: Imatinib mesylate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial Of Imatinib Mesylate (Gleevec®) (NSC-716051) In Combination With Capecitabine (Xeloda®) (NSC-712807) In Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed Response Rate (Complete and Partial) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Number of participants with confirmed complete or partial response. Confirmed response (complete and partial) per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (V1.0). Complete Response (CR) is complete disappearance of all measurable and non-measurable disease; no new lesions; no disease related symptoms; and normalization of markers and other abnormal lab values. Partial response (PR) applies only to patients with at least one measurable lesion. PR is greater than or equal to 30% decrease under baseline of the sum of longest diameter of all target measurable lesions; no unequivocal progression of non-measurable disease and no new lesions. Confirmed response is two or more objective statuses a minimum of four weeks apart documented before progression or symptomatic deterioration.


Secondary Outcome Measures:
  • Progression-free Survival at 6 Months [ Time Frame: Six months ] [ Designated as safety issue: No ]
    Percentage of participants progression-free at 6 months. Progression-free survival (PFS) measured from date of registration to first observation of progressive disease (per RECIST criteria (V1.0)), death due to any cause, or symptomatic deterioration. Kaplan-Meier was used to estimate progression-free survival (PFS) at six months.

  • Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Every 3 weeks while on treatment for up to 3 years. ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported.


Enrollment: 27
Study Start Date: June 2004
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib Mesylate & Capecitabine Drug: Capecitabine
1,000 mg/m^2 by mouth twice daily Days 1-14 of each 21 day cycle
Other Name: Xeloda
Drug: Imatinib mesylate
400 mg by mouth daily
Other Name: Gleevec

Detailed Description:

OBJECTIVES:

  • Determine the confirmed complete and partial response rate in women with progressive stage IV adenocarcinoma of the breast treated with imatinib mesylate and capecitabine.
  • Determine the 6-month progression-free survival of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.
  • Correlate, preliminarily, c-kit and platelet-derived growth factor receptor expression with estrogen and progesterone receptor status, response, survival, and time to disease progression in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate* once daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *If the patient tolerates the starting dose of imatinib mesylate in course 1, the dose will be increased in subsequent courses.

Patients are followed every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-70 patients (25-45 patients with measurable disease and 25 with non-measurable disease) will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • Histologically or cytologically confirmed adenocarcinoma of the breast
  • Stage IV measurable disease
  • Disease progression after at least 1, but no more than 2, prior chemotherapy regimens for metastatic disease
  • Patients with hormone-sensitive tumors must have received prior hormonal therapy
  • Patients with human epidermal growth factor receptor 2 (HER2)/neu-overexpressing tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) should have received trastuzumab (Herceptin®) in the adjuvant or metastatic setting (unless contraindicated)
  • No clinical evidence of or known brain or central nervous system (CNS) disease
  • Hormone Receptor status known
  • Female age 18 and over
  • Performance status Zubrod 0-2
  • Absolute neutrophil count > 1,500/mm^3
  • Leukocyte count > 3,000/mm^3
  • Platelet count > 100,000/mm^3
  • Bilirubin normal
  • aspartate aminotransferase (AST) / alanine aminotransferase (ALT) < 2.5 times upper limit of normal
  • Creatinine normal OR Creatinine clearance > 60 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No history of severe hypersensitivity reaction to compounds of similar chemical or biological composition to imatinib mesylate, capecitabine, or fluorouracil
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No prior biologic therapy (e.g., vaccines)
  • No concurrent filgrastim (G-CSF) for chemotherapy-induced neutropenia
  • No prior capecitabine or fluorouracil for metastatic breast cancer
  • Prior hormonal therapy allowed
  • More than 4 weeks since prior radiotherapy - Previously irradiated area(s) must not be the only site of disease
  • More than 4 weeks since prior major surgery
  • More than 4 weeks since prior therapy for breast cancer
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational or commercial agents or therapies for metastatic breast cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00087152

Sponsors and Collaborators
Investigators
Study Chair: Helen K. Chew, MD University of California, Davis
Study Chair: Kathy S. Albain, MD Loyola University
  More Information

Additional Information:
Publications:
Chew HK, Barlow W, Albain K, et al.: SWOG 0338: a phase II trial of imatinib mesylate in combination with capecitabine in metastatic breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-10529, 2006.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00087152     History of Changes
Other Study ID Numbers: NCI-2012-03033, U10CA032102, S0338, CDR0000372950
Study First Received: July 8, 2004
Results First Received: July 13, 2011
Last Updated: May 12, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Fluorouracil
Imatinib
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014