Saracatinib in Treating Patients With Locally Advanced or Metastatic Stomach or Gastroesophageal Junction Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma

Conditions
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Adenocarcinoma of the Gastroesophageal Junction, Adenocarcinoma of the Stomach, Recurrent Gastric Cancer, Stage III Gastric Cancer, Stage III Esophageal Cancer, Stage IV Esophageal Cancer, Stage IV Gastric Cancer

Intervention / Treatment
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* Drug: saracatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEJ) Tumors of the GEJ must be sub-specified as type I, II, or III using the Siewert classification Metastatic or locally advanced disease Patients with local/regional disease only, must have unresectable 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: Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation Active peptic ulcer disease Short gut syndrome Malabsorption syndrome of any type Total or partial bowel obstruction Inability to tolerate oral medications 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: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia 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 chemotherapy 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (kinase inhibitor therapy)<br>Patients receive saracatinib PO, at a dose of 175 mg QD in the absence of disease progression or unacceptable toxicity. | Drug: saracatinib<br>* Patients receive AZD0530 (saracatinib) PO QD in the absence of disease progression or unacceptable toxicity.<br>* Other names: AZD0530;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria) | PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. CR is defined as disappearance of all non-target lesions and normalization of tumor marker level. | Every 2 weeks for the first 4 weeks, and then every 4-8 weeks thereafter, for at least 16 weeks up to 37 weeks | 
| Prolonged Stable Disease Rate (Defined as Stable Disease for ≥ 16 Weeks) |  | Every 2 weeks for the first 4 weeks, and then every 4-8 weeks thereafter, for at least 16 weeks up to 37 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions,or a measurable increase in non-target lesions, or the appearance of new lesions. | Up to 1 year (median, 6 month, 1-year) | 
| Progression-free Survival | Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible. | Measured from the date of enrollment to progression, death or last contact, or last tumor assessment before the start of further anti-tumor therapy | 
| Median Survival | Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible. | Up to 1 year | 
| Overall Survival | The Kaplan-Meier method will be used to estimate overall and time to progression estimates. Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible. | Up to 1 year (median, 6 months, and 1 year) | 
| Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0. | Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0. | Weekly during treatment | 
| Patient Tolerability | Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible. | Weekly during treatment | 
| Association Between Correlative Markers and Clinical Outcomes | Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible. | At baseline, 6 months, and then at 1 year |