Clinical trial NCT00585221: Study of Imatinib and Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients
Official title: A Phase II Study Combining Targeted Therapy With Immunotherapy Using Imatinib Plus Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Cancer Brain
Solid Tumors
Keywords: Gastrointestinal stromal tumors
Imatinib
Peginterferon α-2b
Immunotherapy
Targeted therapy
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-01-03
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Decrease in Tumor Size.
timeFrame: 18 months
measure: Time to Progression (TTP).
timeFrame: two years
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Lei Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen LL, Chen X, Choi H, Sang H, Chen LC, Zhang H, Gouw L, Andtbacka RH, Chan BK, Rodesch CK, Jimenez A, Cano P, Jones KA, Oyedeji CO, Martins T, Hill HR, Schumacher J, Willmore C, Scaife CL, Ward JH, Morton K, Randall RL, Lazar AJ, Patel S, Trent JC, Frazier ML, Lin P, Jensen P, Benjamin RS. Exploiting antitumor immunity to overcome relapse and improve remission duration. Cancer Immunol Immunother. 2012 Jul;61(7):1113-24. doi: 10.1007/s00262-011-1185-1. Epub 2011 Dec 24.