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

Stage IV Breast Cancer Clinical Trial

Official title:

A Phase II Study of AZD0530 in Hormone Receptor-Negative, Metastatic or Unresectable, Locally Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559507
• Other study ID #: NCI-2009-00191
• Secondary ID: MSKCC-07112N01CM
• Status: Completed
• Phase: Phase 2
• First received: November 15, 2007
• Last updated: April 2, 2014
• Start date: October 2007
• Est. completion date: February 2011

Study information

• Verified date: December 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Other known NCT identifiers

• NCT01645605
• NCT01664481

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• 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

Intervention

Drug:
• saracatinib

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Control Rate (DCR)	DCR defined as complete response (CR), partial response (PR), stable disease (SD) > 24 weeks. Simon's two-stage optimal design was used to estimate the DCR of AZD0530 after 24 weeks of therapy since this design allowed for early termination of the study. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started	After 24 weeks of study therapy	No
Secondary	Overall Response Rate (CR and PR)	Overall Response rate is defined as the sum of the complete response rate and partial response rate. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started	From start of treatment to 24 weeks after completion of study treatment	No
Secondary	Median Time to Treatment Failure		From the start of treatment up to 4 weeks after completion of study treatment	No