Thyroid CancerPhase 2NCT02657551
A Study Using Regorafenib as Second or Third Line Therapy in Metastatic Medullary Thyroid Cancer
A Phase 2 study testing Regorafenib in people with Thyroid Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is studying a targeted therapy as a possible treatment for thyroid cancer. A targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancer
- 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
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2016to 7 Aug 2023
- 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
- Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
- Age ≥ 18 years.
- Life expectancy of at least 12 weeks (3 months).
- Eastern Cooperative Oncology Group performance status of ≤1.
- Histologically or cytologically confirmed diagnosis of metastatic medullary thyroid cancer.
- Documented disease progression within 6 months prior to study registration, as defined by RECIST criteria.
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- Must have at least 1 site of measurable disease by RECIST criteria, by version 1.1.
- Archival tissue block or unstained slides (from primary or metastatic site) must be available, otherwise fresh tissue biopsy sample will be collected.
- Any number of prior chemotherapies and targeted therapies are allowed.
- Patients must have received at least one prior line of targeted therapy.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements within 3 weeks prior to study registration:
- Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate amino-transferease (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
- Alkaline phosphastase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
- Serum creatinine ≤ 1.5 x the ULN
- International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x ULN. (Subjects who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care. (See Section 3.3)
- Platelet count > 100000 /mm3, hemoglobin (Hb) > 9 g/dL, absolute neutrophil count (ANC) 1500/mm3. Blood transfusion to meet the inclusion criteria will not be allowed.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to study registration. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. The definition of adequate contraception will be based on the judgment of the investigator.
- Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 2 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
- Subject must be able to swallow and retain oral medication.
Who cannot join
- Prior treatment with regorafenib.
- Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.
- Active or clinically significant cardiac disease including:
- Congestive heart failure - New York Heart Association (NYHA) > Class II.
- Active coronary artery disease.
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- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
- Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
- Evidence or history of bleeding diathesis or coagulopathy.
- Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
- Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment.
- Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form).
- Patients with pheochromocytoma.
- Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
- Ongoing infection > Grade 2 NCI-CTCAE v4.0.
- Symptomatic metastatic brain or meningeal tumors.
- Presence of a non-healing wound, or non-healing ulcer, (that is not tumor related) or bone fracture.
- Major surgical procedure or significant traumatic injury within 28 days before start of study medication.
- Other investigational treatment during or within 30 days before starting study treatment.
- Use of any approved tyrosine kinase inhibitors within 2 weeks or 6 half-lives of the agen, whichever is shorter, prior to receiving study drug.
- Prior radiation within 14 days before start of study medication.Renal failure requiring hemo-or peritoneal dialysis.
- Dehydration Grade ≥1 NCI-CTCAE v4.0.
- Patients with seizure disorder requiring medication.
- Persistent proteinuria ≥ Grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
- Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.0 Grade 2 dyspnea).
- History of organ allograft (including corneal transplant).
- Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.
- Any malabsorption condition.
- Women who are pregnant or breast-feeding.
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
- Excluded therapies and medications, previous and concomitant
- Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib, other agents being investigated in combination with regorafenib).
- Prior use of regorafenib.
- Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 4 weeks of trial entry (signing of the informed consent form).
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
- Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids.
- --- However, prophylactic anticoagulation as described below is allowed:
- Low dose warfarin (1 mg orally, once daily) with PT-INR ≤ 1.5 x ULN is permitted. Infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy. Therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes.
- Low dose aspirin (≤ 100 mg daily).
- Prophylactic doses of heparin.
- Use of any herbal remedy (e.g. St. John's Wort [Hypericum perforatum])
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Yale Cancer Center
New Haven, Connecticut, 06520-8028
About this study
Official title: A Phase II Study Using Regorafenib as Second or Third Line Therapy in Metastatic Medullary Thyroid Cancer
This research study is studying a targeted therapy as a possible treatment for thyroid cancer. A targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells.
- The name of the study intervention involved in this study is regorafenib.
Read the detailed description
This is a phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has approved regorafenib as a treatment for metastatic colorectal cancer and locally advanced, unresectable or metastatic gastrointestinal stromal tumor. Regorafenib has not been approved for treatment against thyroid cancer.
Regorafenib is an oral anti-tumor agent that blocks activity of a specific kind of protein involved in normal cellular functions and in pathologic processes such as tumor formation and maintenance.
- Conditions
- Thyroid Cancer
- Being tested
- Regorafenib
- Keywords
- Thyroid Cancer
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called Stivarga
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | Regorafenib tablets 80mg orally, once daily at predetermined dosage for 21 days per cycle Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
10-month Progression-free Survival (PFS) Rate [MTC Cohort]
10-month PFS Rate is the proportion of participants ramaing alive and progression free at 10 months. Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Measured: 10 months
Objective Response Rate (ORR) [DTC Cohort]
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Measured: Up to 23.9 months. Tumor assessments were performed at baseline, on Day 1 of Cycle 3, and every 28 days thereafter. After treatment discontinuation, assessments continued every 2 months (±7 days).
Secondary outcomes (2)
Grade 3-5 Toxicity Rate
Grade 3-5 toxicity rate is defined as the proportion of participants who experienced at least one grade 3-5 adverse event (AE) of any type during the time of observation. All AEs were summarized and graded based on CTCAE v4.
Measured: AEs were evaluated on treatment cycle 1 day 1 of week 1, 2 and 3, and cycle 2 day 1 of week 1 and 3, and cycle 3 and beyond day 1 of week 1. For this study cohort, participants were evaluated for AEs for the maximum treatment duration up to 24 months.
Change From Cycle 1 Day 1 in MD Anderson Symptom Inventory-Thyroid (MDASI-Thy) Score
The MDASI-Thy assesses the severity of symptoms, including 13 core symptom items, 6 additional module symptom items, and 6 interference items, at their worst in the past 24 hours using a 0-10 numerical rating scale, where higher scores indicate worse symptoms. For each section (core symptoms, thyroid-specific symptoms, and interference), the section score is calculated as the mean of the item scores and therefore ranges from 0 to 10. Change scores were calculated as the end-of-treatment section score minus the corresponding Cycle 1 Day 1 section score.
Measured: Assessed at Cycle 1 Day 1 and end of treatment. The maximum treatment duration was 23.9 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2016 (estimated)
- Study startJan 2016
- Primary completion7 Aug 2023
- Study completion7 Aug 2023
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 Thyroid CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Kartik Sehgal, MD, Dana-Farber Cancer Institute
- Investigators
- Kartik Seghal, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02657551
- Sponsor's protocol ID
- 15-350
- Status last verified
- Jul 2026
- First submitted
- 9 Nov 2015
- Last updated
- 12 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: There are no plans to share individual participant data. However, at the end of the study, results will be presented and published.
Publications
Ettrich TJ, Seufferlein T. Regorafenib. Recent Results Cancer Res. 2018;211:45-56. doi: 10.1007/978-3-319-91442-8_3.
PubMed 30069758
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Using Regorafenib as Second or Third Line Therapy in Metastatic Medullary Thyroid Cancer
- ClinicalTrials.gov ID
- NCT02657551
- Acronym / sponsor ID
- 15-350
- Conditions
- Thyroid Cancer
- Keywords
- Thyroid Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jan 2016 (actual)
- Primary completion
- 7 Aug 2023 (actual)
- Study completion
- 7 Aug 2023 (actual)
- First posted
- 18 Jan 2016 (estimated)
- Results
- Posted 15 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a targeted therapy as a possible treatment for thyroid cancer. A targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells.
- The name of the study intervention involved in this study is regorafenib.
Detailed description
This is a phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has approved regorafenib as a treatment for metastatic colorectal cancer and locally advanced, unresectable or metastatic gastrointestinal stromal tumor. Regorafenib has not been approved for treatment against thyroid cancer.
Regorafenib is an oral anti-tumor agent that blocks activity of a specific kind of protein involved in normal cellular functions and in pathologic processes such as tumor formation and maintenance.
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 tablets 80mg orally, once daily at predetermined dosage for 21 days per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
- Age ≥ 18 years.
- Life expectancy of at least 12 weeks (3 months).
- Eastern Cooperative Oncology Group performance status of ≤1.
- Histologically or cytologically confirmed diagnosis of metastatic medullary thyroid cancer.
Key exclusion criteria (43 listed)
- Prior treatment with regorafenib.
- Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.
- Active or clinically significant cardiac disease including:
- Evidence or history of bleeding diathesis or coagulopathy.
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: StivargaRegorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes. | Drug | Regorafenib |
Primary outcome
10-month Progression-free Survival (PFS) Rate [MTC Cohort]
Time frame: 10 months
10-month PFS Rate is the proportion of participants ramaing alive and progression free at 10 months. Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Objective Response Rate (ORR) [DTC Cohort]
Time frame: Up to 23.9 months. Tumor assessments were performed at baseline, on Day 1 of Cycle 3, and every 28 days thereafter. After treatment discontinuation, assessments continued every 2 months (±7 days).
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
2 secondary outcomes
Grade 3-5 Toxicity Rate
Time frame: AEs were evaluated on treatment cycle 1 day 1 of week 1, 2 and 3, and cycle 2 day 1 of week 1 and 3, and cycle 3 and beyond day 1 of week 1. For this study cohort, participants were evaluated for AEs for the maximum treatment duration up to 24 months.
Change From Cycle 1 Day 1 in MD Anderson Symptom Inventory-Thyroid (MDASI-Thy) Score
Time frame: Assessed at Cycle 1 Day 1 and end of treatment. The maximum treatment duration was 23.9 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30069758Ettrich TJ, Seufferlein T. Regorafenib. Recent Results Cancer Res. 2018;211:45-56. doi: 10.1007/978-3-319-91442-8_3.
- Individual participant dataSharing planned: No. There are no plans to share individual participant data. However, at the end of the study, results will be presented and published.
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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.
Kartik Seghal, MD principal investigator
Dana-Farber Cancer Institute
2 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 Thyroid Cancer, run by Dana-Farber Cancer Institute at 2 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 20 inclusion and 43 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 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 15 Nov 2023). 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?
10-month Progression-free Survival (PFS) Rate [MTC Cohort] (time frame: 10 months). The study lists 2 primary outcomes in all. 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 NCT02657551, 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 12 Aug 2026; AzTrials last refreshed its copy on 28 Oct 2026.