Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery

NCT ID: NCT00559507

Last Updated: 2014-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2011-02-28

Brief Summary

This phase II trial is studying saracatinib to see how well it works in treating patients with metastatic or locally advanced breast cancer that cannot be removed by surgery. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the disease control rate of AZD0530 (saracatinib) in patients with metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To estimate the efficacy of AZD0530 in terms of overall response rate (complete and partial response) and progression free survival.

II. To describe the toxicity profile of AZD0530 in this patient population. III. To prospectively explore changes in circulating tumor cells from pre-treatment levels in patients receiving AZD0530.

OUTLINE:

Patients receive saracatinib orally (PO) on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Conditions

Estrogen Receptor-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (enzyme inhibitor therapy)

Patients receive saracatinib PO on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

saracatinib

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

saracatinib

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

AZD0530

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed carcinoma of the breast

• Unresectable disease
• Locally advanced or metastatic (American Joint Committee on Cancer [AJCC] stage IV) disease
• Estrogen receptor-negative and progesterone receptor-negative breast cancer defined as < 10% expression by immunohistochemistry (IHC)
• Measurable disease, defined (per Response Evaluation Criteria in Solid Tumors [RECIST]) as ≥ 1 unidimensionally measurable lesion ≥ 20mm by conventional techniques or ≥ 10 mm by spiral computed tomography (CT) scan

• Measurable target lesions must not be in a previously irradiated field
• Patients with locally advanced, unresectable disease must have progression of disease following no more than one first-line chemotherapy regimen
• Patients with evidence of recurrent disease during or within 6 months after adjuvant chemotherapy will be considered to have failed one line of chemotherapy for metastatic disease
• Human epidermal growth factor receptor 2 (HER2)-positive patients, defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) amplification > 2.1, must have received trastuzumab (Herceptin®) in either the adjuvant or metastatic setting and have had recurrence or progression of disease, respectively
• No known brain metastases
• Male and female patients eligible
• Menopausal status not specified
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 (Karnofsky PS 60-100%)
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin > 9 g/dL
• Total bilirubin normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Urine protein creatinine (UPC) ratio must be ≤ 1.0

• Patients with a UPC ratio > 1.0 must have a 24-hour urine protein < 1,000 mg to be eligible for study
• Not pregnant or nursing
• Women of child-bearing potential and men must use adequate contraception (e.g., hormonal or barrier method of birth control or abstinence) prior to, during, and for 8 weeks after completion of study therapy
• Able to understand and willing to sign a written informed consent document
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
• No QTc interval ≥ 500 msecs
• No condition that impairs the ability to swallow AZD0530 tablets, including the following:

• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
• Prior surgical procedures affecting absorption
• Active peptic ulcer disease
• No intercurrent cardiac dysfunction including, but not limited to, any of the following:

• Symptomatic congestive heart failure
• Unstable angina pectoris
• Uncontrolled cardiac arrhythmia
• History of myocardial infarction within 6 months of treatment
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• No severe restrictive or obstructive lung disease according to baseline pulmonary function studies including any of the following pulmonary function test (PFT) parameters:

• Total lung capacity < 60%
• Forced vital capacity < 50%
• Forced expiratory volume in one second (FEV_1) < 50%
• Diffusion capacity of carbon monoxide (DLCO) < 50%
• Resting room air O_2 saturation < 92% or a decline in O_2 saturation > 4% with exercise
• Patients with metastatic disease may have received no more than 1 prior chemotherapy regimen
• No unresolved toxicity ≥ grade 3 from agents received more than 3 weeks earlier
• No chemotherapy, radiotherapy, or investigational therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study
• No luteinizing hormone-releasing hormone agonists within 4 weeks prior to study entry
• More than 7 days since prior and no concurrent use of specifically prohibited cytochrome P 450 3A4 (CYP3A4) agents
• No concurrent megestrol acetate, even when prescribed for appetite stimulation
• No other concurrent investigational or commercial agents for the treatment of breast cancer
• No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
• No concurrent megestrol acetate

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clifford Hudis

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

MSKCC-07112

Identifier Type: -

Identifier Source: secondary_id

N01CM62204

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000574281

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2009-00191

Identifier Type: -

Identifier Source: org_study_id

NCT01645605

Identifier Type: -

Identifier Source: nct_alias

NCT01664481

Identifier Type: -

Identifier Source: nct_alias