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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Gastrointestinal Stromal Tumor

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response defined using the Choi criteria

Outcome Description:

The design method of Thall, Simon and Estey will be used.

Outcome Time Frame:

2 months

Safety Issue:

No

Principal Investigator

Jonathan Trent

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02883

NCT ID:

NCT00091078

Start Date:

September 2005

Completion Date:

Related Keywords:

  • Gastrointestinal Stromal Tumor
  • Gastrointestinal Stromal Tumors

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030