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

• ClinicalTrials.gov Identifier: NCT00607594
• Recruitment Status: Completed
• First Posted: February 6, 2008
• Results First Posted: July 18, 2014
• Last Update Posted: August 23, 2018
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: saracatinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma
• Study Start Date: January 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: April 2012

Arms and Interventions

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 Name: AZD0530

Outcome Measures

Primary Outcome Measures :

1. Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria) [ Time Frame: 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.
2. Prolonged Stable Disease Rate (Defined as Stable Disease for ≥ 16 Weeks) [ Time Frame: 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 :

1. Time to Progression [ Time Frame: 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.
2. Progression-free Survival [ Time Frame: 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.
3. Median Survival [ Time Frame: 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.
4. Overall Survival [ Time Frame: 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.
5. Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0. [ Time Frame: Weekly during treatment ]
   Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.
6. Patient Tolerability [ Time Frame: 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.
7. Association Between Correlative Markers and Clinical Outcomes [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Hamilton Medical Center

Dalton, Georgia, United States, 30720

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada, L8V 5C2

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

McGill University Department of Oncology

Montreal, Quebec, Canada, H2W 1S6

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Heather-Jane Au; University Health Network-Princess Margaret Hospital

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00607594
• Other Study ID Numbers: NCI-2009-00188; PHL-052 ( Other Grant/Funding Number: N01CM17107 ); CDR0000585708 ( Other Grant/Funding Number: N01CM17107 ); PMH-PHL-052 ( Other Grant/Funding Number: N01CM17107 ); N01CM62203 ( U.S. NIH Grant/Contract )
• First Posted: February 6, 2008
• Results First Posted: July 18, 2014
• Last Update Posted: August 23, 2018
• Last Verified: July 2018

Additional relevant MeSH terms:

Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Saracatinib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action