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

Phase 2

Completed

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

Interventions: Drug: saracatinib

Registration Number: NCT00607594

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (kinase inhibitor therapy)	saracatinib	Patients receive saracatinib PO, at a dose of 175 mg QD in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria)	Every 2 weeks for the first 4 weeks, and then every 4-8 weeks thereafter, for at least 16 weeks up to 37 weeks	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.
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

Name	Time	Method
Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.	Weekly during treatment	Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.
Time to Progression	Up to 1 year (median, 6 month, 1-year)	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.
Progression-free Survival	Measured from the date of enrollment to progression, death or last contact, or last tumor assessment before the start of further anti-tumor therapy	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.
Median Survival	Up to 1 year	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.
Overall Survival	Up to 1 year (median, 6 months, and 1 year)	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.
Patient Tolerability	Weekly during treatment	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.
Association Between Correlative Markers and Clinical Outcomes	At baseline, 6 months, and then at 1 year	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.

Trial Locations

Locations (5): Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
University Health Network-Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
Hamilton Medical Center
🇺🇸
Dalton, Georgia, United States
McGill University Department of Oncology
🇨🇦
Montreal, Quebec, Canada