Evaluation of Patients With Bulky GIST Using Sunitinib

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01054911
• Collaborator: Pfizer (Industry)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 71
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tumor	Drug: Sunitinib; Procedure: Surgery	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Trial of Neoadjuvant Sunitinib in Patients With Bulky GIST
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [6 months]

Secondary Outcome Measures

1. 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

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

• University of Alabama at Birmingham
• Pfizer

Investigators

• Principal Investigator: James A. Posey, M.D., University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James Posey, MD, Associate Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT01054911
• Other Study ID Numbers: F090910001; UAB 0855
• First Posted: Jan 22, 2010
• Last Update Posted: Sep 22, 2016
• Last Verified: Aug 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by James Posey, MD, Associate Professor, University of Alabama at Birmingham: GIST; gastrointestinal stromal tumor; gastrointestinal stomach tumor; Sunitinib
• Additional relevant MeSH terms: Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib Pill
Arm/Group Description	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.
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sunitinib Pill
Arm/Group Description	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.
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 80%
>=65 years	1 20%
Sex: Female, Male (Count of Participants)
Female	3 60%
Male	2 40%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neoadjuvant Therapy Plus Surgery	Neoadjuvant Therapy no Surgery
Arm/Group Description	Patients received oral therapy for up to 12 weeks and re-evaluated for response. Favorable tumor reduction resulted surgical extirpation typically with less morbid operative intervention.	Patients received oral therapy for up to 12 weeks. Reassessment demonstrated response, but no surgical intervention
Measure Participants	4	1
Number [participants]	4 80%	1 NaN

2. Secondary Outcome

Title	Measurable Disease Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Sunitinib Pill
Arm/Group Description	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.
Measure Participants	0

3. Secondary Outcome

Title	Alteration in Diffusion and Vascularity Kinetics
Description	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

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Sunitinib Pill
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	February 2010 to March 2012
Arm/Group Title	Sunitinib Pill
Arm/Group Description	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.
All Cause Mortality
	Sunitinib Pill
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib Pill
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Sunitinib Pill
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
neutropenia	2/5 (40%)	2
hyponatremia	1/5 (20%)	1
Cardiac disorders
hypertension	1/5 (20%)	1
Gastrointestinal disorders
diarrhea	3/5 (60%)	4
altered taste	2/5 (40%)	2
mucositis	2/5 (40%)	2
dysphagia	1/5 (20%)	1
constipation	1/5 (20%)	1
gastrointestinal reflux disease	2/5 (40%)	2
vomiting	1/5 (20%)	1
nausea	1/5 (20%)	1
General disorders
fatigue	3/5 (60%)	3
Musculoskeletal and connective tissue disorders
swelling	1/5 (20%)	1
Nervous system disorders
hand and foot syndrome	2/5 (40%)	2
Respiratory, thoracic and mediastinal disorders
shortness of breath	1/5 (20%)	1
Skin and subcutaneous tissue disorders
hyperpigmentation	2/5 (40%)	2

Limitations/Caveats

This Pilot trial was terminated early due sluggish accrual; thereby, resulting in much smaller numbers.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.