Tumor
Conditions
Keywords
GIST, gastrointestinal stromal tumor, gastrointestinal stomach tumor, Sunitinib
Brief summary
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.
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.
Interventions
DRUGSunitinib
All patients will receive sunitinib 37.5 mg p.o. daily for up to 12 weeks to be taken orally.
PROCEDURESurgery
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.
Sponsors
Pfizer
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurable Disease Response Rate | FDG PET scan at baseline and Week 2, CT scan at baseline and Week 12 | Positron electron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) and computed tomography (CT) will be used. None of the participants were analyzed |
| Alteration in Diffusion and Vascularity Kinetics | MRI at baseline, Week 2 and Week 6 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Sunitinib: All patients will receive sunitinib 37.5 mg p.o. daily for up to 12 weeks to be taken orally.
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. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Sunitinib Pill |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Number of Participants With Adverse Events
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Therapy Plus Surgery | Number of Participants With Adverse Events | 4 participants |
| Neoadjuvant Therapy no Surgery | Number of Participants With Adverse Events | 1 participants |
Secondary
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.
Time frame: MRI at baseline, Week 2 and Week 6
Population: Data were not collected
Secondary
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
Time frame: FDG PET scan at baseline and Week 2, CT scan at baseline and Week 12
Population: Data were not collected.