A Phase II Trial of STI571 in the Treatment of Metastatic Gastric Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00068380
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 72
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. This phase II trial is studying how well imatinib mesylate works in treating patients with refractory metastatic and/or unresectable stomach or gastroesophageal junction cancer.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Gastric Cancer; Stage IV Gastric Cancer	Drug: imatinib mesylate; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the response rate, time to tumor progression, and overall survival in patients with metastatic gastric cancer treated with STI571 who have failed one chemotherapy regimen for metastatic disease.

2. To assess the toxicities of STI571 in these patients. III. To obtain preliminary data on molecular correlates to determine clinical efficacy and toxicity.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk [chemonaïve] vs poor risk [1 prior chemotherapy regimen]).

Patients receive oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 1-1.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of STI571 in the Treatment of Metastatic Gastric Cancer
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (imatinib mesylate) Patients receive oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.	Drug: imatinib mesylate; Given orally; Other Names: CGP 57148 Gleevec Glivec ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Response Rate [Up to 6 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by X-Ray, MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

2. Toxicity Summary [Up to 30 days post treatment]

   Toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. Grade 3 and above adverse events possibly, probably or definitely related to treatment.

3. Progression-free Survival [From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 30 days post treatment]

   Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

4. Overall Survival [From first day of treatment to time of death due to any cause, assessed up to 5 years post-treatment]

   Will be summarized using the Kaplan-Meier product-limit estimators.

5. Time to Treatment Failure [From first day of treatment until discontinuation of treatment, assessed up to 30 days post treatment]

   Defined as the time from start of treatment to the discontinuation of treatment for any reason, including disease progression, treatment toxicity, patient preference, or death Will be summarized using the Kaplan-Meier product-limit estimators. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

6. Baseline Gene Expression Levels of the Target Genes (PDGF-R and PDGF), Genes Associated With Induction of Apoptosis (Bcl-2, Bax), and Cell Cycle Regulatory Genes (p53, p21, p27 [Baseline]

   Will summarized overall and according to response and toxicity (if numbers permit), using medians, quartiles and ranges - or if a transformation is found to render the data compatible with the normal assumptions, with means, standard deviations, and confidence intervals. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously established cut-points) and constructing Kaplan-Meier plots.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with metastatic and/or unresectable carcinoma of the stomach, who have measurable disease

• Life expectancy > 3 months

• Karnofsky Performance Status > 60%

• Absence of an active infection

• Granulocyte count of > 1,500/mm^3

• Hemoglobin (Hgb) >= 9 mg/dl

• Serum bilirubin =< 1.5 mg/dl, regardless of liver involvement secondary to tumor

• Platelets > 100,000/mm^3

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x the institutional upper limit of normal

• Calculated creatinine clearance of > 60 ml/min

• Patients must have signed written informed consent

• Female patients of child-bearing potential must have a negative blood or urine pregnancy test within two weeks prior to initial study treatment

• Patients who have had prior chemotherapy or radiation therapy must have recovered from any toxicities prior to study entry

• Patients must have radiographic imaging to document measurable disease within 28 days prior to initial study therapy

Exclusion Criteria:

• Diagnosis of resectable carcinoma of the stomach

• Major surgery within four weeks of study entry

• Brain metastasis or known seizure disorder

• Fertile men and women not using an acceptable method of contraception

• Pregnant or lactating patients are excluded since STI571 may be harmful to the developing fetus and child

• Patients known to be HIV positive and receiving HAART are excluded because of possibly pharmacological interactions

• Active peptic ulceration or active gastrointestinal bleeding or any active bleeding disorders

• Use of therapeutic doses of coumadin (warfarin) as anticoagulation

• Medical, social, or psychological factors which would prevent the patient from completing the treatment protocol

• Patients with serious intercurrent illness which would preclude tolerance and completion of the protocol treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Heinz-Josef Lenz, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00068380
• Other Study ID Numbers: NCI-2012-02825; 5734; N01CM62209
• First Posted: Sep 11, 2003
• Last Update Posted: Jul 11, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Stomach Neoplasms; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	17
COMPLETED	12
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	5 29.4%
Male	12 70.6%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by X-Ray, MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Number [percentage of patients responding]	0

2. Primary Outcome

Title	Toxicity Summary
Description	Toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. Grade 3 and above adverse events possibly, probably or definitely related to treatment.
Time Frame	Up to 30 days post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Grade 3 : Alkaline phosphatase increased	1 5.9%
Grade 3 : Anorexia	1 5.9%
Grade 3 : Constipation	1 5.9%
Grade 3 : Fatigue	1 5.9%
Grade 3 : Hyperglycemia	1 5.9%
Grade 3 : Hemoglobin decreased	1 5.9%
Grade 3 : Hypoxia	1 5.9%
Grade 3 : Abdominal pain	1 5.9%
Grade 3 : Hypophosphatemia	2 11.8%
Grade 3 : Hypokalemia	1 5.9%
Grade 3 : Hyponatremia	1 5.9%
Grade 3 : Packed red blood cell transfusion	3 17.6%

3. Primary Outcome

Title	Progression-free Survival
Description	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 30 days post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Median (95% Confidence Interval) [Months]	1.35

4. Primary Outcome

Title	Overall Survival
Description	Will be summarized using the Kaplan-Meier product-limit estimators.
Time Frame	From first day of treatment to time of death due to any cause, assessed up to 5 years post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Median (95% Confidence Interval) [Months]	3.25

5. Primary Outcome

Title	Time to Treatment Failure
Description	Defined as the time from start of treatment to the discontinuation of treatment for any reason, including disease progression, treatment toxicity, patient preference, or death Will be summarized using the Kaplan-Meier product-limit estimators. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	From first day of treatment until discontinuation of treatment, assessed up to 30 days post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	17
Median (95% Confidence Interval) [Months]	0.98

6. Primary Outcome

Title	Baseline Gene Expression Levels of the Target Genes (PDGF-R and PDGF), Genes Associated With Induction of Apoptosis (Bcl-2, Bax), and Cell Cycle Regulatory Genes (p53, p21, p27
Description	Will summarized overall and according to response and toxicity (if numbers permit), using medians, quartiles and ranges - or if a transformation is found to render the data compatible with the normal assumptions, with means, standard deviations, and confidence intervals. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously established cut-points) and constructing Kaplan-Meier plots.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Gene data were not collected. Due to budget constraints and recent reprioritizations, CTEP closed the study to accrual prior to collection of correlative data.

Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected over a period of 2 years, 2 months.
Adverse Event Reporting Description	"Other" adverse events include all grades and all attributions to treatment not included in "Serious" adverse events table.
Arm/Group Title	Treatment (Imatinib Mesylate)
Arm/Group Description	Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Imatinib Mesylate)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Imatinib Mesylate)
	Affected / at Risk (%)	# Events
Total	8/17 (47.1%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/17 (5.9%)	1
Gastrointestinal disorders
Abdominal pain	3/17 (17.6%)	3
Constipation	1/17 (5.9%)	1
Diarrhea	1/17 (5.9%)	1
Flatulence	1/17 (5.9%)	1
Gastrointestinal disorder	2/17 (11.8%)	2
General disorders
Fatigue	1/17 (5.9%)	1
Fever	1/17 (5.9%)	1
General symptom	1/17 (5.9%)	1
Investigations
Creatinine increased	1/17 (5.9%)	1
Metabolism and nutrition disorders
Anorexia	1/17 (5.9%)	1
Dehydration	2/17 (11.8%)	2
Hypoglycemia	1/17 (5.9%)	1
Nervous system disorders
Ischemia cerebrovascular	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/17 (11.8%)	2
Pneumothorax	1/17 (5.9%)	1
Vascular disorders
Hypotension	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Imatinib Mesylate)
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Haemorrhage NOS	1/17 (5.9%)	1
Hemoglobin decreased	11/17 (64.7%)	17
Lymphangiopathy NOS	1/17 (5.9%)	1
Packed red blood cell transfusion	3/17 (17.6%)	3
Cardiac disorders
Sinus tachycardia	1/17 (5.9%)	1
Eye disorders
Conjunctival disorder	1/17 (5.9%)	1
Eye disorder	1/17 (5.9%)	1
Vision blurred	1/17 (5.9%)	1
Gastrointestinal disorders
Abdominal pain	6/17 (35.3%)	6
Ascites	1/17 (5.9%)	1
Constipation	1/17 (5.9%)	1
Diarrhea	4/17 (23.5%)	4
Dry mouth	2/17 (11.8%)	2
Dyspepsia	2/17 (11.8%)	2
Esophagitis	1/17 (5.9%)	1
Gastrointestinal disorder	2/17 (11.8%)	2
Haematochezia	1/17 (5.9%)	1
Melaena	1/17 (5.9%)	1
Nausea	11/17 (64.7%)	14
Vomiting	8/17 (47.1%)	9
General disorders
Fatigue	10/17 (58.8%)	13
General symptom	10/17 (58.8%)	10
Oedema NOS	4/17 (23.5%)	7
Pain	2/17 (11.8%)	2
Investigations
Alanine aminotransferase increased	4/17 (23.5%)	4
Alkaline phosphatase increased	6/17 (35.3%)	8
Aspartate aminotransferase increased	9/17 (52.9%)	12
Creatinine increased	1/17 (5.9%)	1
Hyperbilirubinemia	4/17 (23.5%)	4
Leukopenia	2/17 (11.8%)	4
Lymphopenia	5/17 (29.4%)	6
Neutrophil count decreased	2/17 (11.8%)	4
Platelet count decreased	1/17 (5.9%)	2
Weight loss	2/17 (11.8%)	2
Metabolism and nutrition disorders
Anorexia	6/17 (35.3%)	9
Dehydration	2/17 (11.8%)	2
Hyperglycemia	3/17 (17.6%)	4
Hyperkalemia	1/17 (5.9%)	1
Hypoalbuminemia	5/17 (29.4%)	9
Hypocalcemia	4/17 (23.5%)	7
Hypoglycemia	1/17 (5.9%)	1
Hypokalemia	3/17 (17.6%)	3
Hyponatremia	3/17 (17.6%)	3
Hypophosphatemia	3/17 (17.6%)	5
Musculoskeletal and connective tissue disorders
Bone pain	1/17 (5.9%)	1
Joint pain	1/17 (5.9%)	1
Musculoskeletal disorder	1/17 (5.9%)	2
Myalgia	1/17 (5.9%)	2
Nervous system disorders
Dizziness	2/17 (11.8%)	2
Peripheral motor neuropathy	2/17 (11.8%)	2
Peripheral sensory neuropathy	1/17 (5.9%)	1
Speech disorder	1/17 (5.9%)	1
Psychiatric disorders
Depression	1/17 (5.9%)	2
Insomnia	1/17 (5.9%)	1
Renal and urinary disorders
Proteinuria	1/17 (5.9%)	1
Urinary retention	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal	1/17 (5.9%)	1
Hypoxia	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Photosensitivity	1/17 (5.9%)	1
Pruritus	1/17 (5.9%)	1
Rash desquamating	1/17 (5.9%)	2
Skin discolouration	1/17 (5.9%)	1
Skin disorder	1/17 (5.9%)	1
Vascular disorders
Hypertension	1/17 (5.9%)	1
Thrombosis	1/17 (5.9%)	1

Limitations/Caveats

In the first stage none of the 17 patients responded (CR/PR) to treatment. Due to budget constraints and recent reprioritizations, CTEP closed the study to accrual.

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.