Study of Imatinib and Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients
Condition: Gastrointestinal Stromal Tumors; Cancer Brain; Solid Tumors
MeSH terms: Neoplasms; Gastrointestinal Stromal Tumors
Intervention: Peginterferon-alpha 2b (PegIFNa2b);; Imatinib
Intervention description: Treatment include PegIFNa2b high dose (3 mcg/kg/wk) X 4 doses and low dose (1.5 mcg/kg/wk) X 18 doses, followed by surgical evaluation to render pt disease free if possible.; Continue imatinib until progression.
Intervention MeSH terms: Peginterferon alfa-2b; Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastrointestinal stromal tumors; Imatinib; Peginterferon α-2b; Immunotherapy; Targeted therapy

Summary:

      Imatinib (IM) has dramatically improved survival of gastrointestinal stromal tumors (GIST).
      However, most patients become resistant to IM in less than two years. This clinical trial
      combines targeted therapy (IM) with immunotherapy (peginterferon α-2b). Hypothesis:
      Apoptosis/necrosis of imatinib-sensitive GIST releases GIST-specific antigens in vivo while
      Peginterferon α-2b fulfills the role of cytokine signal (danger signal), this combination can
      induce effective innate and adaptive anti-GIST immunity, which can eradicate
      imatinib-resistant clones and GIST stem cells via recognition of common antigens shared with
      imatinib-sensitive GIST, leading to improved response rate and remission duration.
    

Eligibility criteria:

        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
             >70%.

          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
             enrollment.

         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
             enrollment.

         11. Patients must have PT (prothrombin time), PTT (partial thromboplastin time) and INR
             (international normalized ratio) < institutional upper limit of normal within 4 weeks
             of enrollment.

         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
             potential.

         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
             corticosteroids.

         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
             hypercoagulability.

         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
             guidelines.

         24. In the opinion of the Principal Investigator the patient is eligible and a good
             candidate for this study.