A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma
A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma
This phase II trial is studying how well saracatinib works in treating patients with locally advanced or metastatic stomach or gastroesophageal junction cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To assess the objective disease control rate (i.e., partial or complete response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or stable disease for ≥ 16 weeks) in patients with locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction treated with AZD0530 (saracatinib).
SECONDARY OBJECTIVES:
I. To assess the median time to disease progression, median overall survival, and 1-year survival rate in these patients.
II. To assess the toxicity of AZD0530 in these patients. III. To evaluate potential predictive markers by assessing pretreatment intratumoral levels of src, Y419 phospho-src (P-Src), and c-terminal src kinase (Csk) in archival tumor biopsies.
OUTLINE:
Patients receive saracatinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at least every 2 months.
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
Metastatic or locally advanced disease
Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral computed tomography (CT) scan
No known brain metastases
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 3 months
Platelet count ≥ 100,000/mm³
Leukocytes ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Hemoglobin > 9 g/dL
Total bilirubin normal
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Urine protein creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection
Exclusion Criteria:
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No condition that potentially impairs the ability to swallow or absorb AZD0530, including any of the following:
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD0530
No QTc prolongation (defined as a QTc interval ≥ 460 msec) or other significant electrocardiogram (ECG) abnormalities
No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
No history of ischemic heart disease, including myocardial infarction
No concurrent cardiac dysfunction including, but not limited to, any of the following:
No other concurrent uncontrolled illness, including ongoing or active infection or psychiatric illness/social situations, that would limit compliance with study requirements
Prior chemotherapy allowed provided it was administered as part of initial curative intent therapy (i.e., neoadjuvant therapy, adjuvant therapy and/or concurrently with radiotherapy) in combination with surgery
At least 4 weeks since prior and no more than 1 line of palliative chemotherapy for advanced disease
At least 4 weeks since prior radiotherapy and recovered
At least 4 weeks since prior major surgery and recovered
No cytochrome 450 3A4 (CYP3A4) active agents or substances for ≥ 7 days before, during, and for ≥ 7 days after completion of study treatment
No other concurrent investigational agents
No other concurrent anticancer therapy
No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients