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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00607594
First received: February 1, 2008
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Every 2 weeks for the first 4 weeks, and then every 4-8 weeks thereafter ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Progression [ Time Frame: Up to 1 year (median, 6 month, 1-year) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 1 year (median, 6 months, and 1 year) ] [ Designated as safety issue: No ]
    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.

  • Safety [ Time Frame: Weekly during treatment ] [ Designated as safety issue: Yes ]
    Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.

  • Tolerability [ Time Frame: Weekly during treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: At baseline, 6 months, and then at 1 year ] [ Designated as safety issue: No ]
    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.


Enrollment: 21
Study Start Date: January 2008
Study Completion Date: April 2012
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00607594

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
Investigators
Principal Investigator: Heather-Jane Au University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00607594     History of Changes
Other Study ID Numbers: NCI-2009-00188, PHL-052, CDR0000585708, PMH-PHL-052, N01CM62203
Study First Received: February 1, 2008
Results First Received: June 19, 2014
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on July 28, 2014