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

Solid Tumors Clinical Trial

Official title:

A Phase II Study Combining Targeted Therapy With Immunotherapy Using Imatinib Plus Peginterferon α-2b in Gastrointestinal Stromal Tumor (GIST) Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00585221
• Other study ID #: IRB_00022172
• Status: Terminated
• Phase: Phase 2
• First received: December 21, 2007
• Last updated: July 23, 2013
• Start date: July 2007
• Est. completion date: July 2009

Study information

• Verified date: July 2013
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer,
• Gastrointestinal Stromal Tumors
• Gastrointestinal Stromal Tumors,
• Neoplasms
• Solid Tumors

Intervention

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.
• Imatinib
Continue imatinib until progression.

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	Schering-Plough

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Time to Progression (TTP).		two years	No