Clinical trial NCT01068769: Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor
Official title: A Multi-center Phase II Study Evaluating the Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST), Resistent or Intolerant to at Least Imatinib and Sunitinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor
Keywords: regorafenib
GIST
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: Fox Chase Cancer Center
name: Oregon Health and Science University
name: Bayer
First posted: 2010-02-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine the safety and activity of regorafenib in participants with advanced gastrointestinal stromal tumor (GIST) if the standard approved therapies, imatinib and sunitinib, have failed to control the disease. Regorafenib is a drug that blocks abnormally active signaling enzymes called "tyrosine kinases" which are important to the growth of GIST. This "tyrosine kinase inhibition" is similar to the way that both imatinib and sunitinib work; however, regorafenib blocks certain additional signaling pathways that are not blocked by imatinib or sunitinib. Regorafenib has been not been tested in GIST participants before this research study.

Detailed description: * In this research study, each planned "cycle" of the study lasts 4 weeks. In the first cycle, participants will come to the clinic on Days 1, 15 and 16. For cycles 2 through 4, they will come to the clinic on Days 1 and 15 of each cycle. For cycle 5 and beyond, they will come to the clinic on Day 1 of each cycle. Repeat tumor imaging will be performed at the end of every 2 cycles during study drug administration (e.g. end of cycles 2, 4, 6, etc.)
* During each cycle, participants will take regorafenib by mouth, once a day in the morning, for 3 weeks followed by one week during which you do not take regorafenib (the "rest period").
* FDG-PET/CT (Positron Emission Tomography) scans are required as part of this study to monitor effects of the study drug on the participant's GIST. The first scan will take place before the first dose of study drug. If the first scan shows that the "tracer sugar" collection is increased in the participant's GIST, they will have up to 5 additional scans performed at different time points throughout their participation in this research study.
* Participants may continue to participate in this research study for as long as they do not have serious side effects or their disease does not get worse.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age at the time of study entry
* Histologically confirmed metastatic and/or unresectable GIST with prior failure of both conventional tyrosine kinase inhibitors, imatinib and sunitinib.
* Measurable disease per RECIST 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion.
* ECOG Performance Status 0 or 1
* Adequate organ and marrow function as outlined in the protocol
* Fully recovered from the acute effects of prior cancer therapy before initiation of study drug
* Patients must be suitable for oral drug administration
* Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug
* Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration

Exclusion Criteria:

* Use of any unapproved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drug
* Participants who have had radiotherapy within 4 weeks prior to study entry
* Major surgery, or significant traumatic injury within 4 weeks prior to study entry
* Presence of symptomatic or uncontrolled brain or central nervous system metastases
* Prior exposure to sorafenib
* Prior exposure to regorafenib
* Known or suspected allergy to the investigational agent or any agent given in association with this trial
* Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy or other primary malignancy is neither currently clinically significant nor requiring active intervention
* Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin)
* History of clinically significant cardiac disease or congestive heart failure \> NYHA class 2. Patients must not have unstable angina or new-onset angina within the last 3 months or myocardial infarction within the past 6 months
* Hypertension as defined by systolic blood pressure 140-159 mmHg or diastolic blood pressure 90-99 mmHg; recurrent or persistent or symptomatic increase by \> 20 mmHg (diastolic) or to systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg if previously within normal limits, despite optimal medical management
* Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication
* Ongoing infection of Grade 3 or higher
* Patients with evidence of, or history of, bleeding diathesis. Any major hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication
* Non-healing wound, ulcer or bone fracture
* Renal failure requiring hemo-or peritoneal dialysis
* Dehydration of Grade 2 or greater
* Persistent proteinuria Grade 3 or higher
* Known history of HIV infection or chronic hepatitis B or C
* Uncontrolled intercurrent illness
* Pregnant or lactating females

Primary outcomes:
measure: Clinical Benefit as Defined by the Composite of Complete Response, Partial Response and Stable Disease Lasting 16 Weeks or More Per RECIST 1.1 as a Measure of Disease Control
timeFrame: 2 years
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From date of enrollment until date of first documented progression or date of death from any cause, whichever came first
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Suzanne George, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ben-Ami E, Barysauskas CM, von Mehren M, Heinrich MC, Corless CL, Butrynski JE, Morgan JA, Wagner AJ, Choy E, Yap JT, Van den Abbeele AD, Solomon SM, Fletcher JA, Demetri GD, George S. Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol. 2016 Sep;27(9):1794-9. doi: 10.1093/annonc/mdw228. Epub 2016 Jul 1.