Imatinib Mesylate in Treating Patients With Metastatic Breast Cancer

Phase II Trial of STI571 in Metastatic Breast Cancer

Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have metastatic breast cancer. Imatinib mesylate may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth

Study Overview

• Status: Completed
• Conditions: Male Breast Cancer; Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: imatinib mesylate

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the efficacy of STI571 in metastatic breast cancer (MBC) that demonstrates expression of CD117 (c-kit) and/ or PDGFR.

SECONDARY OBJECTIVES:

I. To determine the clinical activity of STI571 in MBC with expression of CD117 (ckit) and/ or PDGFR by evaluating progression-free survival (PFS).

II. To determine the toxicity profile and tolerability of STI571 in patients with MBC.

III. To define serum, tissue and imaging surrogate endpoints of activity of STI571 in MBC.

OUTLINE:

Patients receive oral imatinib mesylate twice daily. Treatment continues for at least 8 weeks in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic breast cancer

• Documented expression of CD117 (c-kit) or platelet-derived growth factor receptor

  • Adequate tumor tissue from either the primary tumor and/or metastatic disease available for evaluation
• Must have received prior chemotherapy with an anthracycline (doxorubicin or epirubicin) and/or taxane (paclitaxel or docetaxel) as adjuvant or for advanced disease

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Bone disease may not be only source of measurable disease
  • Pleural or peritoneal ascites are not considered measurable disease
• No known brain metastases

• Hormone receptor status:

  • Not specified
• Female or male
• Not specified
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• More than 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin normal
• AST or ALT no greater than 2.5 times upper limit of normal
• Creatinine normal
• Creatinine clearance at least 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No prior allergic reaction attributed to compounds of similar chemical or biologic composition to imatinib mesylate
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 1 week after study
• No concurrent biologic agents

• No more than 2 prior chemotherapy regimens for metastatic disease

  • Therapy with high-dose regimens or bone marrow transplantation considered 1 regimen
• At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and recovered
• No concurrent chemotherapy
• Prior hormonal therapy for stage IV disease and/or as adjuvant therapy allowed
• At least 4 weeks since prior radiotherapy and recovered
• Prior localized radiotherapy that does not influence the signal of the evaluable lesion is allowed
• At least 2 weeks since prior minor surgery
• At least 4 weeks since prior major surgery
• Recovered from prior surgery
• Low-molecular weight heparin or heparin allowed for anticoagulation
• No concurrent warfarin
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent investigational therapies or agents
• No other concurrent anticancer therapy
• No concurrent intake of cola, orange juice, grapefruit, or orange or grapefruit sections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (imatinib mesylate); Patients receive oral imatinib mesylate twice daily. Treatment continues for at least 8 weeks in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Optional correlative studies; Drug: imatinib mesylate; Given PO; Other Names: Gleevec; CGP 57148; Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective tumor response (CR + PR), as determined by the RECIST criteria	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events		Up to 2 years
Time to progression	Reported using the Kaplan-Meier method with 95% confidence intervals indicated.	Up to 2 years
Overall survival	Reported using the Kaplan-Meier method with 95% confidence intervals indicated.	Up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Massimo Cristofanilli, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): July 1, 2004

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: NCI-2012-02491; N01CM17003 (U.S. NIH Grant/Contract); IDO1-691; CDR0000256915 (Registry Identifier: PDQ (Physician Data Query))