Study of Imatinib and Pegylated Interferon-a 2B in Imatinib-naïve Gastrointestinal Stromal Tumor (GIST) Patients

Study of Imatinib and Pegylated Interferon-a 2B in Imatinib-naïve Gastrointestinal Stromal Tumor (GIST) Patients

Gastrointestinal Stromal Tumor

Terminated

2

Start Date 07/01/2007

Age of Trial (yrs) 16.8

First-line

KIT/PDGFRA inhibitor Immune stimulate

Stimulate the immune system

Specifically GIST and only GIST

HCI 22172

University of Utah

Huntsman Cancer Intitute Information Service (Suzanne)

clinical.trials@hci.utah.edu

(801) 587-9834

Oral IV

This trial was closed pending an internal review on 9/17/2008.

5-16-2009: Data Safety Monitoring Committee decision to permanently suspend new trial enrollment, due to issues related to eligibility criteria.

8/24/2010 PI decision to close trial at recommendation of DSMC & IRB

Objectives

Primary

* To measure the efficacy of the combination targeted therapy and immunotherapy. Time to response, response rate, time to progression, and overall survival are clinical end points.
* To evaluate the safety and tolerability of combination therapy.

Secondary

* To correlate antitumor immunity with clinical response.
* To study the in vivo immune modulatory effect of PEG-intron. In particular, its effects on NK and dendritic cell (DC) activation and serum cytokine profiles.
* To identify biomarkers for predicting prognosis, response to treatment, and antitumor immunity; and to discover new target(s) for therapy.

Inclusion Criteria:
• Patients must be >18 years old.
• Patients must have histologic evidence of GIST confirmed by a pathologist at Huntsman Cancer Institute (HCI).
• A paraffin block or 7 unstained slides must be submitted for genotyping prior to enrollment.
• Stage I, II, and III patients are eligible if the primary tumor is 6 cm or larger. All stage IV metastatic or recurrent GISTs are eligible regardless of the size as long as there is measurable tumor. A PET-CT is recommended.
• Patients must have a Zubrod Performance Status of 0-1 or Karnofsky PS > 70% assessed within 2 weeks of enrollment.
• Patients must have a life expectancy of more than twelve months.
• Patients must have negative serology tests for HIV, Hepatitis B, Hepatitis C, Autoimmune panel (Rheumatoid factor, ANA titer) within 28 days of enrollment.
• Patients must have normal thyroid function tests including TSH, and T4 within 2 weeks of enrollment.
• Patients must have adequate liver function as evidenced by the following: total bilirubin, and AST < institutional upper limit of normal assessed within 2 weeks of enrollment.
• Patients must have adequate renal function as evidenced by a serum creatinine < 2 mg/dl within 2 weeks of enrollment.
• Patients must have adequate bone marrow reserve as evidenced by the following: WBC > 3x109 /L, absolute neutrophil count (ANC) > 1.5 x 109 /L, platelet count > 125 x 109 /L, hemoglobin > 11 within 2 weeks of enrollment.
• Patients must have PT, PTT and INR < institutional upper limit of normal within 2 weeks of enrollment.

Exclusion Criteria:
• Patients must not have received imatinib for metastatic disease. GIST patients who received imatinib as adjuvant treatment in the past, and later developed a recurrence are eligible only if the DFS is > 6 months after completion of adjuvant imatinib.
• 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.
• Patients may not have received chemotherapy within 30 days prior to enrollment.
• Patients must have a negative serum pregnancy test if female of childbearing potential.
• Patients must agree to use an accepted and effective method of contraception while on PEG-intron and for a period of 18 months after completing or discontinuing PEG-intron.
• Patients may not have a primary or secondary autoimmune disorder, or immunodeficiency.
• Patients may not have undergone splenectomy or gastrectomy for any reason. Total gastrectomy usually results in poor tolerance to the recommended dose of imatinib.
• Patients cannot require antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids.
• Patients may not have active ischemic heart disease or cerebrovascular disease, congestive heart failure (NYHA class III or IV), or angina requiring ongoing medications.
• Patients cannot show a history of CNS demyelination, inflammatory disease or hereditary or acquired peripheral neuropathy greater than Grade 2.
• 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 PI.
• Patients cannot be taking coumadin, lovenox or heparin for metallic heart valve or hypercoagulability.