Evaluation of Patients With Bulky GIST Using Sunitinib

Pilot Trial of Neoadjuvant Sunitinib in Patients With Bulky GIST

The primary purpose of this study is to determine if oral (mouth) delivery prior to tumor removal in patients with gastrointestinal stromal tumor (GIST) results in tumor shrinkage allowing for successful surgery. Therapy will be administered orally and the response of the tumor will be assessed using CTs or MRIs.

Study Overview

• Status: Terminated
• Conditions: Tumor
• Intervention / Treatment: Drug: Sunitinib; Procedure: Surgery

Detailed Description

Gastrointestinal stromal tumor (GIST) is a rare cancer affecting primarily the digestive tract and sometimes abdominal cavity in adults. The most common site is the stomach followed by the duodenum and small intestine.

Surgery is the mainstay of therapy for GIST patients whose primary tumor is felt to be resectable. Prior to the introduction of Gleevec, patients with inoperable GIST had essentially no therapeutic options. However, sunitinib trials offer options to patients who are Gleevec resistant or have intolerant GIST. Clinical benefit has been demonstrated with positive results in several sunitinib studies of varying phases.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients more than 19 years old with pathologically proven GIST which is bulky or marginally resectable
• Patients must have at least one bidimensionally measurable disease site of 5 cm or greater not previously irradiated. Bone lesions do not qualify.
• Patients must have an ECOG performance of greater than or equal to 2, with projected survival of at least three months.
• Patients must have adequate laboratory parameters:

Hematologic: Hb >9.0; WBC >3200 and platelets >100,000/mm3; Hepatic: Bilirubin <2.0 and AST within 4 times upper limit of normal; Renal: Creatinine of less than or equal to 1.6 or eGFR greater than or equal to 50 mL/min

• Men and women who are of childbearing potential must practice strict birth control for the duration of the study.
• Women of childbearing potential must be non-lactating and non-pregnant with a negative pregnancy test within two weeks of trial registration.
• The patient, a witness, and attending physician will have signed an IRB-approved informed consent prior to Sunitinib administration.

Exclusion Criteria:

• Known brain metastases or significant pleural effusion or ascites.
• Uncontrolled hypertension, diabetes, or other medical condition.
• Major surgery within 21 days of registration.
• Patients wtih organ grafts with the exception of prior high dose chemotherapy with autologous bone marrow (or stem cell) transplantation.
• History of seizures, central nervous system disorders, dementia, or psychosis that might preclude adequate informed consent or protocol compliance.
• Prior therapy for GIST.
• A history of HIV or hepatitis virus infection.
• Any recent medical condition which, in the opinion of the investigator, makes the patient unsuitable for study participation.
• Patients with impaired kidney function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sunitinib pill; Patients will receive six weeks of sunitinib and then subsequently continue for an additional 6 weeks if the evaluation at 6 weeks shows stable disease or objective response. Restaging CT scans will be performed again after 12 weeks of therapy to determine response in preparation for surgical resection anticipated to occur around week 14-16.	Drug: Sunitinib; All patients will receive sunitinib 37.5 mg p.o. daily for up to 12 weeks to be taken orally.; Other Names: SUTENT (Sunitinib); Procedure: Surgery; Following sunitinib therapy, patients will be evaluated for surgery. It is anticipated that the quality of response will allow for complete resection of residual tumor. Surgical resection, if eligible, will occur around week 14-16.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurable Disease Response Rate	Positron electron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) and computed tomography (CT) will be used. None of the participants were analyzed	FDG PET scan at baseline and Week 2, CT scan at baseline and Week 12
Alteration in Diffusion and Vascularity Kinetics	The Response Evaluation Criteria in Solid Tumors (RECIST) criteria may be insensitive in assessing GIST so the Choi criteria will be used. The Choi criteria accounts for morphologic tumor changes and biologic alterations. Diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast magnetic resonance will be used to find the vascular permeability and apparent diffusion coefficient 9ACD) at baseline, Week 2 and Week 6. Weeks 2 and 6 values will be compared to the baseline values using paired t tests.	MRI at baseline, Week 2 and Week 6

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 20, 2010
• First Submitted That Met QC Criteria: January 21, 2010
• First Posted (Estimate): January 22, 2010

Study Record Updates

• Last Update Posted (Estimate): September 22, 2016
• Last Update Submitted That Met QC Criteria: August 2, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: gastrointestinal stromal tumor; GIST; Sunitinib; gastrointestinal stomach tumor
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: F090910001; UAB 0855 (Other Identifier: Institutional study protocol number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No