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

This study has been terminated.
(PI terminated at the recommendation of DSMC & IRB)
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00585221
First received: December 21, 2007
Last updated: April 8, 2013
Last verified: April 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Stromal Tumors,
Cancer,
Solid Tumors
 Drug: Peginterferon-alpha 2b (PegIFNa2b);
Drug: Imatinib
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Combining Targeted Therapy With Immunotherapy Using Imatinib Plus Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Decrease in Tumor Size. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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).

  • Time to Progression (TTP). [ Time Frame: two years ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: July 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
All participants enrolled in the study.
 Drug: Peginterferon-alpha 2b (PegIFNa2b);
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.
Other Name: Trade name: Peg-Intron
Drug: Imatinib
Continue imatinib until progression.
Other Name: Trade name: gleevec

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00585221

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Schering-Plough
Investigators
Principal Investigator: Lei Chen, MD University of Utah
  More Information

No publications provided by University of Utah

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00585221     History of Changes
Other Study ID Numbers: IRB_00022172
Study First Received: December 21, 2007
Results First Received: June 15, 2012
Last Updated: April 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
Gastrointestinal stromal tumors
Imatinib
Peginterferon α-2b
Immunotherapy
Targeted therapy

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Peginterferon alfa-2b
Interferon-alpha
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013