A Phase II Study Combining Targeted Therapy With Immunotherapy Using Imatinib Plus Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients
1. Patients must be >18 years old.
2. Patients must have histologic evidence of GIST (Gastrointestinal Stromal Tumors).
3. If genotyping was not done, a paraffin block or 7 unstained slides or biopsy
unstained slides is required for genotyping within one week of enrollment.
4. Stage I, II, and III patients are eligible if the primary tumor is 6 centimeter or
larger. All stage IV (4) metastatic or recurrent GIST patients who are imatinib-naïve
are eligible. For stage IV patients who had initial good response to imatinib and
stopped imatinib for 10 months or longer. GIST patients who received imatinib as
"adjuvant" treatment in the past, later developed a recurrence are eligible only if
the DFS is > 6 months after completion of adjuvant imatinib.
5. Patients must have a Zubrod Performance Status of 0-1 or Karnofsky Performance Status
6. Patients must have a life expectancy of more than twelve months.
7. Patients must have negative serology tests for HIV (Human immunodeficiency virus).
Hepatitis B, Hepatitis C, and ANA (antinuclear antibodies) titer have to be within 2
times of upper limit of normal within 28 days of enrollment. Patients must have no
clinical rheumatoid arthritis (RA). RA criteria are as follows: 1) morning stiffness
in and around joints lasting at least 1 hour before maximal improvement; 2) soft
tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3)
swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist
joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of
rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in
hand and/or wrist joints.
Criteria 1 through 4 must have been present for at least 6 weeks. RA is defined by
the presence of 4 or more criteria. Patients must have normal thyroid function tests
(1.5 times of upper and lower normal limit) including TSH (Thyroid-stimulating
Hormone), and T4 (Thyroxine) within 4 weeks of enrollment.
8. Patients must have adequate liver function as evidenced by the following: total
bilirubin, and AST (aspartate aminotransferase) < 2 times of institutional upper
limit of normal assessed within 2 weeks of enrollment. If patient has extensive liver
metastasis which is the main cause of abnormal liver function, this requirement does
not apply. The Principal Investigator can use his or her clinical judgment.
9. Patients must have serum creatinine <2 miligrams/deciliter within 2 weeks of
10. Patients must have WBC (white blood cells) > 3x109 /L, absolute neutrophil count
(ANC) > 1.5 x 109 /L platelet count > 125 x 109 /L, hemoglobin > 11 within 2 weeks of
11. Patients must have PT (prothrombin time), PTT (partial thromboplastin time) and INR
(international normalized ratio) < institutional upper limit of normal within 4 weeks
12. Patients must have no history of malignancy other than atypical melanocytic
hyperplasia, basal or squamous skin cancer or any in situ cancer, lobular carcinoma
of the breast in situ, cervical cancer in situ, Clark I melanoma in situ or have been
continuously disease free for 5 years prior to enrollment.
13. Patients may not have received chemotherapy within 30 days prior to enrollment.
14. Patients must have a negative serum pregnancy test if female of childbearing
15. Patients must agree to use an accepted and effective method of contraception while on
Pegintron and for a period of 18 months after completing or discontinuing Pegintron.
16. Patients may not have autoimmune disorder, or immunodeficiency.
17. Patients may not have undergone splenectomy or gastrectomy for any reason. Total
gastrectomy usually results in poor tolerance to the recommended dose of Imatinib.
18. Patients cannot require antihistamines, non-steroidal anti-inflammatory drugs, or
19. Patients may not have active ischemic heart disease or cerebrovascular disease,
congestive heart failure (New York Heart Association class III or IV), or angina
requiring ongoing medications. EKG (Electrocardiography) may not show acute ischemic
changes or acute heart rhythm changes.
20. Patients cannot show a history of Central Nervous System demyelination, inflammatory
disease or hereditary or acquired peripheral neuropathy greater than Grade 2.
21. Patients cannot have an ongoing psychiatric disorder, surgical condition, or medical
condition requiring a treatment regimen that may interfere with the completion of
this trial or the evaluation of safety and efficacy of the study compound. For any
questions, please contact the study Principal Investigator.
22. Patients cannot be taking coumadin, lovenox or heparin for metallic heart valve or
23. Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
24. In the opinion of the Principal Investigator the patient is eligible and a good
candidate for this study.