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

Adenocarcinoma of the Gastroesophageal Junction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00607594
• Other study ID #: NCI-2009-00188
• Secondary ID: PHL-052CDR000058
• Status: Completed
• Phase: Phase 2
• Start date: January 2008
• Est. completion date: April 2012

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: April 2012
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Adenocarcinoma of the Stomach
• Esophageal Neoplasms
• Recurrent Gastric Cancer
• Stage III Esophageal Cancer
• Stage III Gastric Cancer
• Stage IV Esophageal Cancer
• Stage IV Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• saracatinib
Patients receive AZD0530 (saracatinib) PO QD in the absence of disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	Hamilton Medical Center	Dalton	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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