Clinical trial NCT00559507: Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery
Official title: A Phase II Study of AZD0530 in Hormone Receptor-Negative, Metastatic or Unresectable, Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-11-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: After 24 weeks of study therapy
Secondary outcomes:
measure: Overall Response Rate (CR and PR)
timeFrame: From start of treatment to 24 weeks after completion of study treatment
measure: Median Time to Treatment Failure
timeFrame: From the start of treatment up to 4 weeks after completion of study treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Clifford Hudis
role: PRINCIPAL_INVESTIGATOR
References: