Gastrointestinal Stromal TumorPhase 2NCT01068769
Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor
A Phase 2 study testing regorafenib in people with Gastrointestinal Stromal Tumor, run by Suzanne George, MD at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumor
- What is being tested?
- regorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2010to Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Oregon Health Sciences University
Portland, Oregon, 97239
About this study
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
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.
Read the 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.
- Conditions
- Gastrointestinal Stromal Tumor
- Being tested
- regorafenib
- Keywords
- regorafenib, GIST
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
regorafenibDrug
Also called Stivarga
Taken orally, once a day in the morning for 3 weeks followed by a one week rest period
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | Regorafenib adminstered orally, 160 mg per day on days 1 through 21 of a 28 day cycle Receives: Drug: regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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. This is for target lesions. Complete response is disappearance of all target lesions and partial response is >+30% decrease in the sum of the longest diameter of target lesions. Stable disease is neither shrinkage by greater than or equal to 30% of the sum of the longest diameter of target lesions or the increase of lesions by greater than or equal to 20% of the sum of the longest diameter of target lesions. Progressive disease is considered an increase of the sum of the longest diameter of target lesions by greater than or equal to 20%.
Measured: 2 years
Secondary outcomes (1)
Progression-free Survival (PFS)
Progression-free survival is defined as the duration of time from start of study drug administration to time of objective disease progression or death due to any cause, whichever comes first. Progression is evaluated every 8 weeks using Response Criteria for Solid Tumors (RECIST) 1.1. Objective disease progression is defined as a 20% increase in the sum of the longest diameter of target lesion(s).
Measured: From date of enrollment until date of first documented progression or date of death from any cause, whichever came first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionJun 2012
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal Stromal TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Suzanne George, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Fox Chase Cancer Center, Oregon Health and Science University, Bayer
- Responsible party
- Sponsor-investigator, Suzanne George, MD, Dana-Farber/Brigham and Women's Cancer Center
- Investigators
- Suzanne George, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01068769
- Sponsor's protocol ID
- 09-400
- Status last verified
- Aug 2020
- First submitted
- 12 Feb 2010
- Last updated
- 24 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27371698
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01068769
- Acronym / sponsor ID
- 09-400
- Conditions
- Gastrointestinal Stromal Tumor
- Keywords
- regorafenib, GIST
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Suzanne George, MDUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, Fox Chase Cancer Center, Oregon Health and Science University, Bayer
- Study start
- Feb 2010 (actual)
- Primary completion
- Jun 2012 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 15 Feb 2010 (estimated)
- Results
- Posted 24 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: regorafenibRegorafenib adminstered orally, 160 mg per day on days 1 through 21 of a 28 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| regorafenibAlso: StivargaTaken orally, once a day in the morning for 3 weeks followed by a one week rest period | Drug | Regorafenib |
Primary outcome
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
Time frame: 2 years
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. This is for target lesions. Complete response is disappearance of all target lesions and partial response is >+30% decrease in the sum of the longest diameter of target lesions. Stable disease is neither shrinkage by greater than or equal to 30% of the sum of the longest diameter of target lesions or the increase of lesions by greater than or equal to 20% of the sum of the longest diameter of target lesions. Progressive disease is considered an increase of the sum of the longest diameter of target lesions by greater than or equal to 20%.
1 secondary outcome
Progression-free Survival (PFS)
Time frame: From date of enrollment until date of first documented progression or date of death from any cause, whichever came first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27371698Ben-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanne George, MD principal investigator
Dana-Farber Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing regorafenib in people with Gastrointestinal Stromal Tumor, run by Suzanne George, MD at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01068769, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2020.