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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00607594
• Collaborator: (none)
• Enrollment: 21
• Locations: 5
• Arm: 1
• Duration (Months): 51
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

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:

1. 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:

1. To assess the median time to disease progression, median overall survival, and 1-year survival rate in these patients.

2. 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
• 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: Jan 1, 2008
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Apr 1, 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 Names: AZD0530

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hamilton Medical Center	Dalton	Georgia	United States	30720
2	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
3	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
4	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
5	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00607594
• Other Study ID Numbers: NCI-2009-00188; PHL-052; CDR0000585708; PMH-PHL-052; N01CM62203
• First Posted: Feb 6, 2008
• Last Update Posted: Aug 23, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Saracatinib

Study Results

Participant Flow

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 57.1%
>=65 years	9 42.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	6 28.6%
Male	15 71.4%
Region of Enrollment (participants) [Number]
Canada	21 100%

Outcome Measures

1. Primary Outcome

Title	Objective Tumor Response (Defined as Partial [PR] or Complete Response [CR] by RECIST Criteria)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	21
Number [participants]	0 0%

2. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	21
Number [participants]	1 4.8%

3. Secondary Outcome

Title	Time to Progression
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO, at a dose of 175 mg QD in the absence of disease progression or unacceptable toxicity. saracatinib: Patients receive AZD0530 (saracatinib) PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	21
Median (95% Confidence Interval) [months]	1.8

4. Secondary Outcome

Title	Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

Only 17 patients were evaluable for response

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	17
Median (95% Confidence Interval) [months]	1.8

5. Secondary Outcome

Title	Median Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO, at a dose of 175 mg QD in the absence of disease progression or unacceptable toxicity. saracatinib: Patients receive AZD0530 (saracatinib) PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	21
Median (95% Confidence Interval) [months]	7.8

6. Secondary Outcome

Title	Overall Survival
Description	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)

Outcome Measure Data

Analysis Population Description

Only 17 patients were evaluable for response

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	17
Median (95% Confidence Interval) [months]	7.8

7. Secondary Outcome

Title	Highest Grade Toxicity as Assessed by the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.
Description	Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0.
Time Frame	Weekly during treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity. saracatinib laboratory biomarker analysis: Correlative studies
Measure Participants	21
Number [highest grade]	3

8. Secondary Outcome

Title	Patient Tolerability
Description	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

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

9. Secondary Outcome

Title	Association Between Correlative Markers and Clinical Outcomes
Description	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

Outcome Measure Data

Analysis Population Description

data were not collected

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

Adverse Events

Arm/Group Title	Treatment (Kinase Inhibitor Therapy)
Arm/Group Description	Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity. saracatinib laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Kinase Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Kinase Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	8/21 (38.1%)
Blood and lymphatic system disorders
Anemia	1/21 (4.8%)
Gastrointestinal disorders
Esophageal hemorrhage	1/21 (4.8%)
General disorders
Death NOS	2/21 (9.5%)
Fatigue	1/21 (4.8%)
Infections and infestations
Infections and infestations - Other, specify	1/21 (4.8%)
Lung infection	2/21 (9.5%)
Injury, poisoning and procedural complications
Tracheal obstruction	1/21 (4.8%)
Investigations
Blood bilirubin increased	1/21 (4.8%)
Metabolism and nutrition disorders
Hypoalbuminemia	1/21 (4.8%)
Dehydration	1/21 (4.8%)
Hypophosphatemia	1/21 (4.8%)
Hyponatremia	1/21 (4.8%)
Psychiatric disorders
Confusion	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/21 (4.8%)
Hypoxia	2/21 (9.5%)
Dyspnea	2/21 (9.5%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/21 (4.8%)
Vascular disorders
Hypertension	1/21 (4.8%)
Thromboembolic event	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Treatment (Kinase Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	21/21 (100%)
Blood and lymphatic system disorders
Anemia	18/21 (85.7%)
Gastrointestinal disorders
Constipation	15/21 (71.4%)
Anorexia	13/21 (61.9%)
General disorders
Fatigue	14/21 (66.7%)
Investigations
Lymphocyte count decreased	14/21 (66.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.