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

Sponsor:	University of Utah
Information provided by:	University of Utah
ClinicalTrials.gov Identifier:	NCT00585221

Purpose

Tumor tissue from the patient's original diagnostic biopsy or surgery will be evaluated by a pathologist at the Huntsman Cancer Institute to confirm diagnosis. It will also be used to test for KIT mutations.

Condition	Intervention	Phase
Cancer	Drug: Pegylated Interferon-a 2B	Phase II

Study Type:	Interventional
Study Design:	Open Label, Single Group Assignment
Official Title:	A Phase II Study Combining Targeted Therapy With Immunotherapy Using Imatinib Plus Pegylated Interferon-a 2B in Imatinib-naïve Gastrointestinal Stromal Tumor (GIST) Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Interferon alfa-2a Interferon alfa-2b Imatinib Imatinib mesylate Interferon alfa-n1 Interferons

U.S. FDA Resources

Further study details as provided by University of Utah:

Primary Outcome Measures:

Response will be measured by both response evaluation criteria in solid tumors (RECIST) and Choi criteria (10% decrease in unidimensional tumor size or a 15% decrease in tumor density on contrast-enhanced CT scan) (28, 29). [ Time Frame: May 2007-July 2013 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

There is extensive experience with each of these agents used alone at the above prescribed doses and schedule. Imatinib is well-tolerated with mild myelosuppression and some GI distress as the most common adverse events (AEs). Interferon α is a biologic. [ Time Frame: May 2007-July 2013 ] [ Designated as safety issue: No ]

Enrollment:	9
Study Start Date:	July 2007
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1	Drug: Pegylated Interferon-a 2B Peripheral blood monocytes (PBMCs) will be drawn by leukapheresis at baseline (pre-treatment), weeks 3 and 24 (prior to surgery within 7 days), 8 weeks, and at 2 and 4 years are optional among the long-term continuous responders

Detailed Description:

This is an investigator-initiated institutional study that has partial funding support from Schering Plough. Initially all patients will be started on imatinib at a dose of 400 mg per day. If the testing on the original tumor sample indicates the absence of KIT exon 11 mutation, the imatinib dose will be increased to 800 mg per day. Imatinib will continue daily until disease progression. PEG-intron will be given at a dose of 3 mcg/kg as a subcutaneous (under the skin) injection weekly for 4 weeks, and then decreased to 1 mcg/kg subcutaneously weekly for 18 weeks thereafter.

If the patient has resectable disease by CT scan at 24 weeks, along with the surgeon's opinion that the patient can be surgically rendered disease-free, the patient will undergo surgery at that time.

If 4 of the first 15 patients or 6 patients total during the trial experience unexpected severe (grade 4) adverse event (SAE) despite dose attenuation down to PEG-intron dose of 1 mcg/kg, then the trial will be terminated.

A maximum of 30 patients will be enrolled in this study. The anticipated accrual rate is 15 to 30 patients per year, with a follow up of 3 years after completion of 49 22 weeks of PEG-intron treatment of the last patient; the maximum trial duration is 6 years. Participants will be male and female and must be age 18 years or older.

Leukapheresis will be performed prestudy and at week 24 to collect lymphocytes and dendritic cells for research purposes. For each sample, anti-tumor immunity by IFN-γ ELISPOT and immune modulatory effects of PEG-intron by NK & DC cell activation and cytokine profile will be evaluated. Additional leukapheresis procedures may be performed at weeks 3 and 8; and at years 2 and 4 for patients responding to treatment. These additional leukapheresis procedures are optional. The decision to perform additional leukapheresis will be based upon individual patient circumstances.

Patients will remain on study for approximately 4 years. Total study duration will be approximately 6 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

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

Investigators

Principal Investigator:

Lei Chen, MD

University of Utah

More Information

No publications provided

Responsible Party:	Univerisity of Utah ( University of Utah )
Study ID Numbers:	HCI 22172, IRB#: 00022172
Study First Received:	December 21, 2007
Last Updated:	July 17, 2009
ClinicalTrials.gov Identifier:	NCT00585221 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Anti-Infective Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Neoplasms by Site
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Interferon-alpha
Digestive System Neoplasms

Growth Substances
Interferons
Enzyme Inhibitors
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Imatinib
Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Gastrointestinal Stromal Tumors
Interferon Alfa-2b

ClinicalTrials.gov processed this record on November 27, 2009