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Oblimersen and Imatinib Mesylate in Treating Patients With Advanced Gastrointestinal Stromal Tumors That Cannot Be Removed By Surgery

Primary Purpose

Gastrointestinal Stromal Tumor

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
oblimersen sodium
imatinib mesylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: A pre-imatinib paraffin block of tumor or 20 unstained slides should be submitted for correlative studies if available All patients must have either "limited" progression on imatinib (arm 1, some but not all tumor foci progressing and are not amenable to local therapy) or "generalized" progression (arm 2, widespread progression of all tumor foci) after adequate therapy with imatinib mesylate (> or = 400 mg/day for at least 6 weeks) Histologically confirmed diagnosis of Kit-expressing advanced GIST; advanced GIST is defined by patients who have disease that is unresectable; this includes patients with metastatic disease or primary tumors that cannot be safely removed by a sarcoma surgical oncologist Measurable disease by CT; tests used to assess disease must be done within 28 days prior to registration. If a targeted lesion has been previously embolized or irradiated, or if the patient has received imatinib, there must be objective evidence of progression to be considered for response assessment ECOG performance status 0-2 At least 4 weeks and recovery from effects of prior therapy (i.e radiation, biotherapy, chemotherapy other than imatinib mesylate, or embolization;) recovery from the effects of prior therapy such that they are less than or equal to grade 1 in severity for non-hematological toxicities excluding nausea and vomiting controlled with standard anti-emetic regimens, alopecia, fatigue, and peripheral edema Absolute neutrophil count (ANC) >= 1000/mm3 Platelets >= 100,000/mm3 Serum creatinine =< 1.5 x ULN Serum bilirubin =< 1.5 x ULN Serum SGOT or SGPT =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver metastases are present PT and PTT =< 1.5 x ULN Understand and sign written informed consent in accordance with institutional and federal guidelines All patients must have progressive disease defined as 1) an increase in unidimensional tumor size of > or = 10% AND did not meet criteria for PR by CT density, 2) any new lesions, including new tumor nodules in a previous cystic tumor Patients with widespread metastatic and progressive disease will be eligible for this protocol Patients without widespread metastases will be evaluated by a sarcoma surgical oncologist to determine the benefit of and risk of surgical resection; if surgical resection is not recommended, the patient will be eligible for therapy with the study drug Pregnancy or lactation; women or men of reproductive potential must agree to use an effective barrier contraceptive method during treatment and for three months after the last dose of drug; women of reproductive potential must have a negative serum pregnancy test within 7 days prior to registration; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-child bearing potential Exclusion Criteria: Significant concurrent medical disease other than cancer including: New York Heart Association class III or IV cardiac problems (e.g., congestive heart failure, acute myocardial infarction within 2 months of study) Uncontrolled chronic renal or liver disease Uncontrolled diabetes Uncontrolled seizure disorder Active uncontrolled infection, e.g., HIV Organ allografts History of second cancer, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 or more years

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (oblimersen sodium and imatinib mesylate)

Arm Description

Patients receive oblimersen IV continuously on days 1-14. Patients also receive oral imatinib mesylate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Response defined using the Choi criteria
The design method of Thall, Simon and Estey will be used.
Toxicity defined as any of the following events: regimen-related death, transaminitis, infection, or leukopenia grade 3 or higher using NCI CTCAE version 3.0
The design of Thall, Simon and Estey will be used.

Secondary Outcome Measures

Disease-free survival
Regression analyses will be performed to assess the ability of patient prognostic factors to predict these time-to-event outcomes (survival analyses), as well as the probabilities of response and toxicity (logistic or extended logistic regression analyses).
Overall survival
Regression analyses will be performed to assess the ability of patient prognostic factors to predict these time-to-event outcomes (survival analyses), as well as the probabilities of response and toxicity (logistic or extended logistic regression analyses).

Full Information

First Posted
September 7, 2004
Last Updated
June 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00091078
Brief Title
Oblimersen and Imatinib Mesylate in Treating Patients With Advanced Gastrointestinal Stromal Tumors That Cannot Be Removed By Surgery
Official Title
A Phase IIA Study to Determine the Safety and Efficacy of A NCI-Supplied Agent: G3139 (NSC 683428, IND 58842) and Imatinib Mesylate in Patients With Refractory or Relapsed Gastrointestinal Stromal Tumor
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Study Start Date
September 2005 (undefined)
Primary Completion Date
July 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Oblimersen may help imatinib mesylate kill more tumor cells by making tumor cells more sensitive to the drug. This phase II trial is studying how well giving imatinib mesylate together with oblimersen works in treating patients with advanced gastrointestinal stromal tumor that cannot be removed by surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the efficacy of G3139 (bcl-2 antisense oligonucleotide) plus imatinib mesylate in GIST patients with limited or generalized progression after therapy with imatinib. II. To assess the safety of G3139 plus imatinib mesylate in GIST patients with limited or generalized progression after therapy with imatinib. III. To determine whether expression of BCL-2 correlates with survival, time to progression or response rate in patients with GIST treated with G3139 plus imatinib. OUTLINE: This is a multicenter study. Patients are stratified according to extent of disease progression (limited vs generalized). Patients receive oblimersen IV continuously on days 1-14. Patients also receive oral imatinib mesylate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 96 patients (48 per stratum) will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (oblimersen sodium and imatinib mesylate)
Arm Type
Experimental
Arm Description
Patients receive oblimersen IV continuously on days 1-14. Patients also receive oral imatinib mesylate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
oblimersen sodium
Other Intervention Name(s)
augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Other Intervention Name(s)
CGP 57148, Gleevec, Glivec
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response defined using the Choi criteria
Description
The design method of Thall, Simon and Estey will be used.
Time Frame
2 months
Title
Toxicity defined as any of the following events: regimen-related death, transaminitis, infection, or leukopenia grade 3 or higher using NCI CTCAE version 3.0
Description
The design of Thall, Simon and Estey will be used.
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
Regression analyses will be performed to assess the ability of patient prognostic factors to predict these time-to-event outcomes (survival analyses), as well as the probabilities of response and toxicity (logistic or extended logistic regression analyses).
Time Frame
Up to 4 years
Title
Overall survival
Description
Regression analyses will be performed to assess the ability of patient prognostic factors to predict these time-to-event outcomes (survival analyses), as well as the probabilities of response and toxicity (logistic or extended logistic regression analyses).
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A pre-imatinib paraffin block of tumor or 20 unstained slides should be submitted for correlative studies if available All patients must have either "limited" progression on imatinib (arm 1, some but not all tumor foci progressing and are not amenable to local therapy) or "generalized" progression (arm 2, widespread progression of all tumor foci) after adequate therapy with imatinib mesylate (> or = 400 mg/day for at least 6 weeks) Histologically confirmed diagnosis of Kit-expressing advanced GIST; advanced GIST is defined by patients who have disease that is unresectable; this includes patients with metastatic disease or primary tumors that cannot be safely removed by a sarcoma surgical oncologist Measurable disease by CT; tests used to assess disease must be done within 28 days prior to registration. If a targeted lesion has been previously embolized or irradiated, or if the patient has received imatinib, there must be objective evidence of progression to be considered for response assessment ECOG performance status 0-2 At least 4 weeks and recovery from effects of prior therapy (i.e radiation, biotherapy, chemotherapy other than imatinib mesylate, or embolization;) recovery from the effects of prior therapy such that they are less than or equal to grade 1 in severity for non-hematological toxicities excluding nausea and vomiting controlled with standard anti-emetic regimens, alopecia, fatigue, and peripheral edema Absolute neutrophil count (ANC) >= 1000/mm3 Platelets >= 100,000/mm3 Serum creatinine =< 1.5 x ULN Serum bilirubin =< 1.5 x ULN Serum SGOT or SGPT =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver metastases are present PT and PTT =< 1.5 x ULN Understand and sign written informed consent in accordance with institutional and federal guidelines All patients must have progressive disease defined as 1) an increase in unidimensional tumor size of > or = 10% AND did not meet criteria for PR by CT density, 2) any new lesions, including new tumor nodules in a previous cystic tumor Patients with widespread metastatic and progressive disease will be eligible for this protocol Patients without widespread metastases will be evaluated by a sarcoma surgical oncologist to determine the benefit of and risk of surgical resection; if surgical resection is not recommended, the patient will be eligible for therapy with the study drug Pregnancy or lactation; women or men of reproductive potential must agree to use an effective barrier contraceptive method during treatment and for three months after the last dose of drug; women of reproductive potential must have a negative serum pregnancy test within 7 days prior to registration; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-child bearing potential Exclusion Criteria: Significant concurrent medical disease other than cancer including: New York Heart Association class III or IV cardiac problems (e.g., congestive heart failure, acute myocardial infarction within 2 months of study) Uncontrolled chronic renal or liver disease Uncontrolled diabetes Uncontrolled seizure disorder Active uncontrolled infection, e.g., HIV Organ allografts History of second cancer, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 or more years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Trent
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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Oblimersen and Imatinib Mesylate in Treating Patients With Advanced Gastrointestinal Stromal Tumors That Cannot Be Removed By Surgery

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