Regorafenib and Nivolumab in Mismatch Repair (MMR) Refractory Colorectal Cancer

NCT03712943 | Completed Phase 1 FDA Drug

• 1 other identifier: MCC-19581
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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 (MMR) proficiency.

Conditions

Colorectal Cancer; Metastatic Colorectal Cancer; Colon Cancer

Keywords

colon cancer; colorectal; MMR; Mismatch Repair

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  To determine the maximum tolerated dose of Regorafenib in combination with Nivolumab in advanced, refractory colorectal cancers.

  Up to 12 months

Secondary Outcomes (3)

• Response Rate

  Every 2nd cycle (Cycles are 28 days) up to 12 months

• Overall Survival (OS)

  Up to 24 months after conclusion of treatment

• Frequency and Severity of Adverse Events

  Up to 12 months

Study Arms (2)

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.

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.

Drug: Regorafenib; Drug: Nivolumab

Interventions

Regorafenib DRUG

Regorafenib orally 80 mg daily for 21 days (3 weeks on, 1 week off).

Also known as: Stivarga

Regorafenib and Nivolumab Combination - Escalation; Regorafenib and Nivolumab Combination - Expansion

Nivolumab DRUG

Nivolumab 240 mg administered intravenously every 2 weeks.

Also known as: OPDIVO

Regorafenib and Nivolumab Combination - Escalation; Regorafenib and Nivolumab Combination - Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• 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.

  PMID: 35526308 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Interventions

regorafenib; Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dae W Kim, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Regorafenib and Nivolumab

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 19, 2018
• Study Start: October 23, 2018
• Primary Completion: September 1, 2021
• Study Completion: January 18, 2024
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)