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

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.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Gastroesophageal Junction; Stage IV Gastric Cancer; Recurrent Gastric Cancer; Stage III Gastric Cancer; Adenocarcinoma of the Stomach; Stage IV Esophageal Cancer; Stage III Esophageal Cancer
• Intervention / Treatment: Drug: saracatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
• United States
  • Georgia
    • Dalton, Georgia, United States, 30720
      • Hamilton Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Heather-Jane Au, University Health Network-Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 1, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimate): February 6, 2008

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Neoplasms; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Saracatinib
• Other Study ID Numbers: NCI-2009-00188; N01CM62203 (U.S. NIH Grant/Contract); PHL-052 (Other Grant/Funding Number: N01CM17107); CDR0000585708 (Other Grant/Funding Number: N01CM17107); PMH-PHL-052 (Other Grant/Funding Number: N01CM17107)