Clinical trial NCT00607594: Saracatinib in Treating Patients With Locally Advanced or Metastatic Stomach or Gastroesophageal Junction Cancer
Official title: A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-02-06
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria)
timeFrame: Every 2 weeks for the first 4 weeks, and then every 4-8 weeks thereafter, for at least 16 weeks up to 37 weeks
measure: Prolonged Stable Disease Rate (Defined as Stable Disease for ≥ 16 Weeks)
timeFrame: 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 outcomes:
measure: Time to Progression
timeFrame: Up to 1 year (median, 6 month, 1-year)
measure: Progression-free Survival
timeFrame: Measured from the date of enrollment to progression, death or last contact, or last tumor assessment before the start of further anti-tumor therapy
measure: Median Survival
timeFrame: Up to 1 year
measure: Overall Survival
timeFrame: Up to 1 year (median, 6 months, and 1 year)
measure: Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.
timeFrame: Weekly during treatment
measure: Patient Tolerability
timeFrame: Weekly during treatment
measure: Association Between Correlative Markers and Clinical Outcomes
timeFrame: At baseline, 6 months, and then at 1 year
Other outcomes:
Locations:
city: Dalton
country: United States
facility: Hamilton Medical Center
state: Georgia
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
Study officials:
affiliation: University Health Network-Princess Margaret Hospital
name: Heather-Jane Au
role: PRINCIPAL_INVESTIGATOR
References: