Colorectal CancerPhase 1NCT03712943
Regorafenib and Nivolumab in Mismatch Repair (MMR) Refractory Colorectal Cancer
A Phase 1 study testing Regorafenib and Nivolumab in people with Colorectal Cancer and Metastatic Colorectal Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The main purpose of this study is to test the safety, tolerable side effects, and determine the highest tolerable dose of the combination of Regorafenib and Nivolumab. Researchers want to find out if this combination of Regorafenib and Nivolumab can help people with metastatic colorectal cancer with mismatch repair… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Metastatic Colorectal Cancer, Colon Cancer
- What is being tested?
- Regorafenib and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2018to 18 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically confirmed diagnosis of colorectal adenocarcinoma
- Proficient DNA mismatch repair (MMR) or stable microsatellite disease.
- Participants with the presence of at least one lesion with measurable disease as defined by 10mm in longest diameter for a soft tissue lesions or 15mm in short axis for a lymph node by RECIST 1.1 for response assessment.
- Participants must have received and progressed through or become intolerant to fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab, and if K-ras wild type, cetuximab or panitumumab containing therapies. Exceptions may apply.
- Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1
- Estimated life expectancy over 3 months.
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- Adequate bone marrow, liver and renal function.
- Participants must not have had chemotherapy, major surgery, monoclonal antibody therapy or experimental therapy within the 21 days prior to the start of regorafenib and nivolumab administration
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) performed within 24 hours prior to the start of study drug and then every 4 weeks. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.
- Participants (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the Informed Consent Form (ICF) until at least 5 months for females and 7 months for males after the last dose of study drug
- Participants must be able to understand and be willing to sign the written informed consent form and be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study requirements.
Who cannot join
- Participants with active Central Nervous System (CNS) metastases If CNS metastases are treated and participants are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a Brain MRI prior to enrollment.
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v5.0] on repeated measurement) despite optimal medical management.
- Active or clinically significant cardiac disease.
- Women who are pregnant or breast-feeding
- Prior therapy with regorafenib, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
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- Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Ascites, pleural effusion, or pericardial fluid requiring drainage in the last 4 weeks
- Participants with phaeochromocytoma
- Ongoing infection > Grade 2
- Presence of a non-healing wound, or bone fracture.
- Renal failure requiring hemo-or peritoneal dialysis.
- Seizure disorder requiring medication.
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
- Pleural effusion or ascites that causes respiratory compromise.
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
- 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.
- Persistent proteinuria ≥ Grade 3
- History of organ allograft
- Participants requiring warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon)
- Participants with a condition requiring a strong CYP3A4 inhibitors or strong CYP3A4 inducers.
- Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy or procedure, excluding alopecia.
- Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
- Participants with an arterial thrombotic or thromboembolic event within 6 months of informed consent.
- Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection.
- Child-Pugh B cirrhosis (or worse) or a history of hepatic encephalopathy
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Major surgery or a wound that has not fully healed within 4 weeks of enrollment.
- Participants requiring concurrent anti-cancer therapy other than study treatment.
- Participants requiring hormonal therapy during the study or within 2 weeks of first study enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase I Study of Regorafenib and Nivolumab in Mismatch Repair (MMR) Proficient Advanced Refractory Colorectal Cancer
The main purpose of this study is to test the safety, tolerable side effects, and determine the highest tolerable dose of the combination of Regorafenib and Nivolumab. Researchers want to find out if this combination of Regorafenib and Nivolumab can help people with metastatic colorectal cancer with mismatch repair (MMR) proficiency.
- Being tested
- Regorafenib, Nivolumab
- Keywords
- colon cancer, colorectal, MMR, Mismatch Repair
- Medical subject headings
- Colorectal Neoplasms, Colonic 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 orally 80 mg daily for 21 days (3 weeks on, 1 week off).
NivolumabDrug
Also called OPDIVO
Nivolumab 240 mg administered intravenously every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib and Nivolumab Combination - Escalation | Experimental | Dose Escalation: To find the dose of regorafenib that can be safely given with nivolumab in patients with advanced, refractory colorectal cancers. Receives: Drug: Regorafenib; Drug: Nivolumab |
| Regorafenib and Nivolumab Combination - Expansion | Experimental | Dose Expansion: To find the effect on tumor of the combination of regorafenib and nivolumab. Receives: Drug: Regorafenib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
To determine the maximum tolerated dose of Regorafenib in combination with Nivolumab in advanced, refractory colorectal cancers.
Measured: Up to 12 months
Secondary outcomes (3)
Response Rate
To access response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Measured: Every 2nd cycle (Cycles are 28 days) up to 12 months
Overall Survival (OS)
Occurrence of Overall Survival
Measured: Up to 24 months after conclusion of treatment
Frequency and Severity of Adverse Events
To evaluate the frequency and severity of adverse events and tolerability of the combination regimen.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start23 Oct 2018
- Primary completion1 Sep 2021
- Study completion18 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Regorafenib and Nivolumab
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Dae W Kim, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03712943
- Sponsor's protocol ID
- MCC-19581
- Status last verified
- Feb 2026
- First submitted
- 15 Oct 2018
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kim RD, Kovari BP, Martinez M, Xie H, Sahin IH, Mehta R, Strosberg J, Imanirad I, Ghayouri M, Kim YC, Kim DW. A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer. Eur J Cancer. 2022 Jul;169:93-102. doi: 10.1016/j.ejca.2022.03.026. Epub 2022 May 5.
PubMed 35526308
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Regorafenib and Nivolumab in Mismatch Repair (MMR) Proficient Advanced Refractory Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03712943
- Acronym / sponsor ID
- MCC-19581
- Keywords
- colon cancer, colorectal, MMR, Mismatch Repair
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 23 Oct 2018 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 18 Jan 2024 (actual)
- First posted
- 19 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to test the safety, tolerable side effects, and determine the highest tolerable dose of the combination of Regorafenib and Nivolumab. Researchers want to find out if this combination of Regorafenib and Nivolumab can help people with metastatic colorectal cancer with mismatch repair (MMR) proficiency.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Regorafenib and Nivolumab
| Arm | Type | Receives |
|---|---|---|
| Regorafenib and Nivolumab Combination - Escalation | Experimental | Drug: Regorafenib, Drug: NivolumabDose Escalation: To find the dose of regorafenib that can be safely given with nivolumab in patients with advanced, refractory colorectal cancers. |
| Regorafenib and Nivolumab Combination - Expansion | Experimental | Drug: Regorafenib, Drug: NivolumabDose Expansion: To find the effect on tumor of the combination of regorafenib and nivolumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed diagnosis of colorectal adenocarcinoma
- Proficient DNA mismatch repair (MMR) or stable microsatellite disease.
- Participants with the presence of at least one lesion with measurable disease as defined by 10mm in longest diameter for a soft tissue lesions or 15mm in short axis for a lymph node by RECIST 1.1 for response assessment.
- Participants must have received and progressed through or become intolerant to fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab, and if K-ras wild type, cetuximab or panitumumab containing therapies. Exceptions may apply.
- Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1
Key exclusion criteria (31 listed)
- Participants with active Central Nervous System (CNS) metastases If CNS metastases are treated and participants are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a Brain MRI prior to enrollment.
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v5.0] on repeated measurement) despite optimal medical management.
- Active or clinically significant cardiac disease.
- Women who are pregnant or breast-feeding
- Prior therapy with regorafenib, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
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 orally 80 mg daily for 21 days (3 weeks on, 1 week off). | Drug | Regorafenib and Nivolumab Combination - Escalation, Regorafenib and Nivolumab Combination - Expansion |
| NivolumabAlso: OPDIVONivolumab 240 mg administered intravenously every 2 weeks. | Drug | Regorafenib and Nivolumab Combination - Escalation, Regorafenib and Nivolumab Combination - Expansion |
Primary outcome
Maximum Tolerated Dose
Time frame: Up to 12 months
To determine the maximum tolerated dose of Regorafenib in combination with Nivolumab in advanced, refractory colorectal cancers.
3 secondary outcomes
Response Rate
Time frame: Every 2nd cycle (Cycles are 28 days) up to 12 months
Overall Survival (OS)
Time frame: Up to 24 months after conclusion of treatment
Frequency and Severity of Adverse Events
Time frame: Up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Derived from this study: PubMed 35526308Kim RD, Kovari BP, Martinez M, Xie H, Sahin IH, Mehta R, Strosberg J, Imanirad I, Ghayouri M, Kim YC, Kim DW. A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer. Eur J Cancer. 2022 Jul;169:93-102. doi: 10.1016/j.ejca.2022.03.026. Epub 2022 May 5.
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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.
Dae W Kim, MD principal investigator
H. Lee Moffitt Cancer Center and Research 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 Regorafenib and Nivolumab in people with Colorectal Cancer and Metastatic Colorectal Cancer, run by H. Lee Moffitt Cancer Center and Research 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 11 inclusion and 31 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 9 Feb 2026. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (time frame: Up to 12 months). 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 NCT03712943, 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 9 Feb 2026.