Adenocarcinoma of the Gastroesophageal Junction, Adenocarcinoma of the Stomach, Recurrent Gastric Cancer, Stage III Esophageal Cancer, Stage III Gastric Cancer, Stage IV Esophageal Cancer, Stage IV Gastric Cancer
Conditions
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.
Interventions
DRUGsaracatinib
Patients receive AZD0530 (saracatinib) PO QD in the absence of disease progression or unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria) | 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 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. |
| Median Survival | 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. |
| Overall Survival | 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. |
| Patient Tolerability | 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. |
| Association Between Correlative Markers and Clinical Outcomes | 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. |
| Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0. | Weekly during treatment | Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0. |
| Time to Progression | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Kinase Inhibitor Therapy) Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Treatment (Kinase Inhibitor Therapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 63 years |
| Region of Enrollment Canada | 21 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 8 / 21 |
Outcome results
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.
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria) | 0 participants |
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Prolonged Stable Disease Rate (Defined as Stable Disease for ≥ 16 Weeks) | 1 participants |
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.
Time frame: At baseline, 6 months, and then at 1 year
Population: data were not collected
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.
Time frame: Weekly during treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0. | 3 highest grade |
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.
Time frame: Up to 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Median Survival | 7.8 months |
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.
Time frame: Up to 1 year (median, 6 months, and 1 year)
Population: Only 17 patients were evaluable for response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Overall Survival | 7.8 months |
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.
Time frame: Weekly during treatment
Population: Data were not collected
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.
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
Population: Only 17 patients were evaluable for response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Progression-free Survival | 1.8 months |
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.
Time frame: Up to 1 year (median, 6 month, 1-year)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Kinase Inhibitor Therapy) | Time to Progression | 1.8 months |