Gastrointestinal Stromal TumorPhase 1SURENCT02164240
Phase Ib Study of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable GIST
A Phase 1 study testing Sunitinib and Regorafenib in people with Gastrointestinal Stromal Tumor, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
The purpose of this research study is to determine the safety and tolerability of sunitinib alternating with regorafenib in participants with advanced gastrointestinal stromal tumor GIST, if the standard approved therapies (imatinib, sunitinib and regorafenib) 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?
- Sunitinib and Regorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to May 2021
- Phase
- Phase 1
- 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. Patients must demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line and beyond). Any number of previous therapies for GIST is allowed.
- Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area is ineligible to be considered as measurable disease unless there is objective evidence of progression of the lesion prior to study enrollment.
- ECOG performance status 0 or 1 (see Appendix A).
- Participants must have adequate organ and marrow function as outlined in the protocol.
- Patients must be able to swallow oral medication.
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- 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.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Use of any approved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drugs.
- Patients with intolerance to sunitinib and/or regorafenib.
- 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.
- Known or suspected allergy to the investigational agent or any agent given in association with this trial.
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- 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). Patients with controlled atrial fibrillation are not excluded.
- History of clinically significant cardiac disease or congestive heart failure > NYHA class 2 (See Appendix C). Patients must not have unstable angina (anginal symptoms at rest) 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 mmHg or diastolic blood pressure > 90 mmH 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 (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the start of study medication).
- Patients with evidence or history of any bleeding diathesis, irrespective of severity.
- Ongoing infection ≥ Grade 2.
- Patients with any seizure disorder requiring medication.
- Non-healing wound, ulcer, or bone fracture.
- Persistent proteinuria Grade 2 or higher measured by urine protein:creatinine ratio on a urine sample or during 24-hour assessment.
- HIV-positive individuals on combination antiretroviral therapy.
- Patients with active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
- Uncontrolled intercurrent illness.
- Pregnant or lactating females.
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.
- Strong CYP3A4 inhibitors within 28 days or 5 drug half-lives, whichever is longer, before start of study drug.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Non-randomized, Open-label Phase Ib Study of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Progressing After Prior Therapy With Tyrosine Kinase Inhibitors
The purpose of this research study is to determine the safety and tolerability of sunitinib alternating with regorafenib in participants with advanced gastrointestinal stromal tumor GIST, if the standard approved therapies (imatinib, sunitinib and regorafenib) have failed to control the disease. Additionally, this study seeks to determine the highest dose that can be given safely for this combination of drugs.
Read the detailed description
This is a non-randomized, open label, single-center, single-arm, phase Ib study to evaluate the safety and the preliminary efficacy of short cycles of sunitinib alternated with regorafenib in participants with metastatic and/or unresectable gastrointestinal stromal tumor GISTs with prior failure of tyrosine kinase inhibitors (TKI). The study consists of two cohorts: a dose-escalation, dose-finding cohort, and dose-expansion cohort. Between 6 to 15 patients are expected to be included in the escalation cohort. A total of 20 eligible and evaluable patients will be included in the expansion cohort to further assess toxicity and evaluate preliminary efficacy.
Each treatment cycle lasts 28 days (4 weeks), during which time you will be taking the study drug, sunitinib, for the first 3 days of the week, followed by the study drug, regorafenib, for the last 4 days of the week. The study drugs will be taken continuously for 4 weeks each cycle, unless the study team instructs you otherwise. Each participant will receive a study diary. The diary will also include special instructions for taking the study drugs.
- Conditions
- Gastrointestinal Stromal Tumor
- Being tested
- Sunitinib, Regorafenib
- Keywords
- Gastrointestinal Stromal Tumor
- 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.
SunitinibDrug
Also called Sutent
Intervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops.
RegorafenibDrug
Also called Stivarga
Intervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib alternated with Regorafenib | Experimental | The treatment cycle is defined as 28 days. Treatment consists of 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each cycle. The starting dose level is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage and recommended phase II dose is determined. An alternative scheme of 4-week cycles of the same regimen but with 21 days of dosing followed by 7 days of rest will be studied in case of toxicities during d 22-28 of the starting 4-weeks continuous cycles. Tumor assessments performed at baseline and after every two dosing cycles to assess response. Toxicity monitored throughout the study. Receives: Drug: Sunitinib; Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious and Non-Serious Adverse Events
Dose-escalation cohort is to determine the frequency and characteristics of DLTs of alternation of sunitinib and regorafenib at each dose level during the first cycle of therapy. Toxicity will be graded accordingly with NCI CTCAE version 4.0
Measured: Up to Day 28
Secondary outcomes (2)
Percentage of Participants With Clinical Benefit
Percentage of participants who experienced complete response, partial response or stable disease per RECIST 1.1 at 16 weeks
Measured: 16 weeks
Median Progression Free Survival (mPFS)
Non-parametric Kaplan-Meier analysis to assess median progression free survival (mPFS)
Measured: From date of registration until date of protocol-defined progression while on this protocol, assessed up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2014 (estimated)
- Study startJul 2014
- Primary completionDec 2016
- Study completionMay 2021
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.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Suzanne George, MD, Dana-Farber Cancer Institute
- Investigators
- Suzanne George, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02164240
- Sponsor's protocol ID
- 14-149
- Acronym
- SURE
- Status last verified
- May 2021
- First submitted
- 12 Jun 2014
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Serrano C, Leal A, Kuang Y, Morgan JA, Barysauskas CM, Phallen J, Triplett O, Marino-Enriquez A, Wagner AJ, Demetri GD, Velculescu VE, Paweletz CP, Fletcher JA, George S. Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7287-7293. doi: 10.1158/1078-0432.CCR-19-2150. Epub 2019 Aug 30.
PubMed 31471313
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomized, Open-label Phase Ib Study of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Progressing After Prior Therapy With Tyrosine Kinase Inhibitors
- ClinicalTrials.gov ID
- NCT02164240
- Acronym / sponsor ID
- SURE / 14-149
- Conditions
- Gastrointestinal Stromal Tumor
- Keywords
- Gastrointestinal Stromal Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Bayer, Pfizer
- Study start
- Jul 2014 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 16 Jun 2014 (estimated)
- Results
- Posted 12 Sep 2019
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 tolerability of sunitinib alternating with regorafenib in participants with advanced gastrointestinal stromal tumor GIST, if the standard approved therapies (imatinib, sunitinib and regorafenib) have failed to control the disease. Additionally, this study seeks to determine the highest dose that can be given safely for this combination of drugs.
Detailed description
This is a non-randomized, open label, single-center, single-arm, phase Ib study to evaluate the safety and the preliminary efficacy of short cycles of sunitinib alternated with regorafenib in participants with metastatic and/or unresectable gastrointestinal stromal tumor GISTs with prior failure of tyrosine kinase inhibitors (TKI). The study consists of two cohorts: a dose-escalation, dose-finding cohort, and dose-expansion cohort. Between 6 to 15 patients are expected to be included in the escalation cohort. A total of 20 eligible and evaluable patients will be included in the expansion cohort to further assess toxicity and evaluate preliminary efficacy.
Each treatment cycle lasts 28 days (4 weeks), during which time you will be taking the study drug, sunitinib, for the first 3 days of the week, followed by the study drug, regorafenib, for the last 4 days of the week. The study drugs will be taken continuously for 4 weeks each cycle, unless the study team instructs you otherwise. Each participant will receive a study diary. The diary will also include special instructions for taking the study drugs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib alternated with Regorafenib | Experimental | Drug: Sunitinib, Drug: RegorafenibThe treatment cycle is defined as 28 days. Treatment consists of 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each cycle. The starting dose level is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage and recommended phase II dose is determined. An alternative scheme of 4-week cycles of the same regimen but with 21 days of dosing followed by 7 days of rest will be studied in case of toxicities during d 22-28 of the starting 4-weeks continuous cycles. Tumor assessments performed at baseline and after every two dosing cycles to assess response. Toxicity monitored throughout the study. |
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. Patients must demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line and beyond). Any number of previous therapies for GIST is allowed.
- Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area is ineligible to be considered as measurable disease unless there is objective evidence of progression of the lesion prior to study enrollment.
- ECOG performance status 0 or 1 (see Appendix A).
- Participants must have adequate organ and marrow function as outlined in the protocol.
Key exclusion criteria (23 listed)
- Use of any approved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drugs.
- Patients with intolerance to sunitinib and/or regorafenib.
- 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.
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 |
|---|---|---|
| SunitinibAlso: SutentIntervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | Sunitinib alternated with Regorafenib |
| RegorafenibAlso: StivargaIntervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | Sunitinib alternated with Regorafenib |
Primary outcome
Number of Participants With Serious and Non-Serious Adverse Events
Time frame: Up to Day 28
Dose-escalation cohort is to determine the frequency and characteristics of DLTs of alternation of sunitinib and regorafenib at each dose level during the first cycle of therapy. Toxicity will be graded accordingly with NCI CTCAE version 4.0
2 secondary outcomes
Percentage of Participants With Clinical Benefit
Time frame: 16 weeks
Median Progression Free Survival (mPFS)
Time frame: From date of registration until date of protocol-defined progression while on this protocol, assessed up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31471313Serrano C, Leal A, Kuang Y, Morgan JA, Barysauskas CM, Phallen J, Triplett O, Marino-Enriquez A, Wagner AJ, Demetri GD, Velculescu VE, Paweletz CP, Fletcher JA, George S. Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7287-7293. doi: 10.1158/1078-0432.CCR-19-2150. Epub 2019 Aug 30.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sunitinib and Regorafenib in people with Gastrointestinal Stromal Tumor, run by Dana-Farber Cancer Institute at 1 site 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 23 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 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 12 Sep 2019). 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?
Number of Participants With Serious and Non-Serious Adverse Events (time frame: Up to Day 28). 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 NCT02164240, 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 14 Jun 2021.