Study of Imatinib and Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients

NCT00585221 | Terminated Phase 2 Results DMC

• 1 other identifier: IRB_00022172
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Stromal Tumors; Cancer Brain; Solid Tumors

Keywords

Gastrointestinal stromal tumors; Imatinib; Peginterferon α-2b; Immunotherapy; Targeted therapy

Outcome Measures

Primary Outcomes (2)

• Decrease in Tumor Size.

  Response rate is measured by PET-CT scan (a decrease in standardized uptake value (SUV) by 25%), Response Evaluation Criteria in Solid Tumors (RECIST), and Choi criteria (10% decrease in tumor size or a 15% decrease in tumor density on contrast-enhanced CT, computed tomography, scan).

  18 months

• Time to Progression (TTP).

  two years

Study Arms (1)

All patients

EXPERIMENTAL

All participants enrolled in the study.

Drug: Peginterferon-alpha 2b (PegIFNa2b);; Drug: Imatinib

Interventions

Peginterferon-alpha 2b (PegIFNa2b); DRUG

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.

Also known as: Trade name: Peg-Intron

All patients

Imatinib DRUG

Continue imatinib until progression.

Also known as: Trade name: gleevec

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Utah: lead
• Schering-Plough: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 22198309 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Brain Neoplasms

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Huntsman Cancer Institute

candace.larson@hci.utah.edu

801-213-4241

Study Officials

• Lei Chen, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 3, 2008
• Study Start: July 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: February 10, 2017
• Results First Posted: November 21, 2012

Record last verified: 2016-12

Locations

US (1)