A Trial to Learn Whether Regorafenib in Combination With Nivolumab Can Improve Tumor Responses and How Safe it is for Participants With Solid Tumors

NCT ID: NCT04704154

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-03
• Study Completion Date: 2024-03-29

Brief Summary

Researchers are looking for a better way to treat people with solid tumors. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works.

In this trial, the researchers want to learn about regorafenib taken together with nivolumab in a small number of participants with different types of tumors. These include tumors in the head and neck, the esophagus, the pancreas, the brain, and the biliary tract. The biliary tract includes gall bladder and bile ducts.

The trial will include about 200 participants who are at least 18 years old. All of the participants will take 90 mg of regorafenib as a tablet by mouth. The dose of regorafenib can be adjusted up to 120 mg or down to 60 mg by the doctor based on how well a participant tolerates treatment. All of the participants will receive 480 milligrams (mg) of nivolumab through a needle put into a vein (IV infusion).

The participants will take treatments in 4-week periods called cycles. They will take regorafenib once a day for 3 weeks, then stop for 1 week. In each cycle, the participants will receive nivolumab one time. These 4-week cycles will be repeated throughout the trial. The participants can take nivolumab and regorafenib until their cancer gets worse, until they have medical problems, or until they leave the trial. The longest nivolumab can be given is up to 2 years.

During the trial, the doctors will take pictures of the participants' tumors using CT or MRI and will take blood and urine samples. The doctors will also do physical examinations and check the participants' heart health using an electrocardiogram (ECG). They will ask questions about how the participants are feeling and if they have any medical problems.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regorafenib+Nivolumab

Parallel-cohort in adult participants with selected recurrent or metastatic tumors (HNSCC, ESCC, PDAC, BTC, and GBM/AA) who have been previously treated with one or more systemic therapy for the selected tumor indication.

Group Type: EXPERIMENTAL

Regorafenib, (Stivarga, BAY73-4506)

Intervention Type: DRUG

Intake orally, starting with 3x 30 mg tablets every day (once daily.) for 21 days of every 28-day cycle (21 days on, 7 days off).

If the starting dose is well tolerated dose can be escalated to 120 mg (4x30 mg tablets).

Nivolumab (Opdivo)

Intervention Type: DRUG

480 mg administered on Day 1 of each treatment cycle.

Interventions

Regorafenib, (Stivarga, BAY73-4506)

Intake orally, starting with 3x 30 mg tablets every day (once daily.) for 21 days of every 28-day cycle (21 days on, 7 days off).

If the starting dose is well tolerated dose can be escalated to 120 mg (4x30 mg tablets).

Intervention Type: DRUG

Nivolumab (Opdivo)

480 mg administered on Day 1 of each treatment cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed selected recurrent or metastatic solid tumor types that have progressed after treatment with standard therapies and for which there are no curative intent surgery or chemoradiation.
• Cohort 1: subjects with HNSCC (Head and neck squamous-cell carcinoma) who have not received prior PD-1/PD-L1 inhibitor therapy.
• Cohort 2: subjects with HNSCC who have progressed on or after prior systemic therapy, at least one of which included a PD-1/PD-L1 inhibitor alone or in combination with chemotherapy.
• Cohort 3: subjects with ESCC (Esophageal Squamous Cell Carcinoma) who progressed on or after platinum and/or fluoropyrimidine based regimen.
• Cohort 4: subjects with PDAC (Pancreatic ductal adenocarcinoma) who have progressed on or after gemcitabine or fluoropyrimidine based regimens.
• Cohort 5: subjects with BTC (Biliary tract carcinoma) (intrahepatic or extrahepatic cholangiocarcinoma or gall bladder cancer) who have progressed on gemcitabine or fluoropyrimidine or platinum therapy or a combination of these agents.
• Cohort 6: subjects with Grade IV GBM (Glioblastoma multiforme) or Grade III AA (Anaplastic astrocytoma) (World Health Organization [WHO] criteria) with unequivocal first progression after surgery followed by radiotherapy and temozolomide.
• Documented HPV (Human papilloma virus) / p16 status for oropharyngeal cancer.
• Capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Adult participants of legal maturity (18 years or older).
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1.
• Adequate hematologic and organ function as assessed by the following laboratory tests performed within 7 d before start of study treatment including:

• Total bilirubin ≤1.5 x the upper limit of normal (ULN). Total bilirubin (≤3 x ULN) is allowed if Gilbert's syndrome is documented
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN (≤5 x ULN for participants with liver involvement of their cancer)
• Measurable disease by baseline CT or MRI per RECIST 1.1 or RANO.
• Participants must consent to provide recent biopsy/tumor tissue of a primary tumor lesion or from metastases (e.g. liver, lung) for HNSCC (IO treated) for Stage 1 and 2 and in HNSCC (IO naïve) cohort for Stage 2.
• Anticipated life expectancy greater than 3 months.
• Be able to swallow and absorb oral tablets.

Exclusion Criteria

• Presence of symptomatic central nervous system (CNS) metastases, leptomeningeal metastases or spinal cord compression. Previously-treated lesions should be stable for at least 6 weeks prior to study entry.
• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment.
• Prior therapy with PD-1/PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of immunotherapy to treat cancer (except cohort 2).
• Cohort 2: More than one prior therapy with PD-1/PD-L1 or CTLA-4 inhibitors, or any other form of immunotherapy to treat cancer.
• ESCC:

• patients with apparent tumor invasion on organs located adjacent to the esophageal disease (e.g., the aorta or respiratory tract).
• patients who have previously received taxane agents for recurrent/metastatic cancer.
• GBM/AA

• Primary tumors localized to the brainstem or spinal cord.
• Presence of diffuse leptomeningeal disease or extracranial disease.
• Participants requiring > 4 mg of dexamethasone or biologic equivalent per day to control symptoms related to brain tumor and cerebral edema within 21 days of starting study treatment.
• Participants who have known dMMR/MSI-H cancers or NTRK (tropomyosin receptor kinase) fusions.
• Prior therapy with regorafenib.
• Systemic anti-cancer treatment within 14 days or less than 5 half-lives (whichever is shorter) of the first dose of study treatment.
• Participants who have permanent discontinuation of PD-1/PD-L1 therapy due to toxicity.
• Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study treatment. Active pulmonary emboli or deep vein thrombosis that are significant or not adequately controlled on anticoagulation regimen as per investigator's judgement.
• History of cardiac disorders as defined by:

• Congestive heart failure ≥ New York Heart Association (NYHA) class 2:
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), myocardial infarction less than 6 months before start of study drug.
• Uncontrolled cardiac arrhythmias.
• Poorly controlled hypertension, defined as a blood pressure consistently above 140/90 mmHg despite optimal medical management.
• Participants with an active, known or suspected autoimmune disease.
• History of (non-infectious) pneumonitis that required steroids, current pneumonitis or interstitial lung disease.
• Active infection > NCI-CTCAE Grade 2.
• Positive test (from historical data or tested during screening) for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating presence of virus, e.g. Hepatitis B surface antigen (HBsAg, Australia antigen) positive (except for participants on anti-viral therapy for HBV with a viral load < 100 IU/mL), or Hepatitis C antibody (anti-HCV) positive (except if HCV-ribonucleic acid [RNA] negative).
• Pregnancy or breast feeding.
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with the participation for the full duration of the trial.
• Participants with a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol Myers Squibb Co. and Ono Pharmaceutical Co., Ltd

UNKNOWN

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope - Duarte Cancer Center

Duarte, California, United States

Rocky Mountain Cancer Centers / Aurora, CO

Aurora, Colorado, United States

Moffitt Cancer Center

Tampa, Florida, United States

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Baylor Charles A. Sammons Cancer Center at Dallas

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Hôpital Erasme/Erasmus Ziekenhuis

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

CHU de Liège

Liège, , Belgium

Institut Bergonie - Unicancer Nouvelle Aquitaine

Bordeaux, , France

UNICANCER - Centre Leon Berard (CLB)

Lyon, , France

APHP-Hopital la Pitie Salpetriere

Paris, , France

Institut de Cancerologie Ouest - Saint-Herblain

Saint-Herblain, , France

Institut Claudius Regaud - iUCT Oncopole

Toulouse, , France

Gustave Roussy - Departement Oncologie-Radiotherapie

Villejuif, , France

AUSL di Bologna_Istituto delle Scienze Neurologiche - UO Oncologia del Sistema Nervoso

Bologna, Emilia-Romagna, Italy

IRCCS Foundation Istituto Neurologico Carlo Besta

Milan, Lombardy, Italy

Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia

Rozzano, Lombardy, Italy

Istituto Oncologico Veneto_Padova - UOC Oncologia 1

Padua, Veneto, Italy

ASST Grande Ospedale Metropolitano Niguarda - Oncologia Falck

Milan, , Italy

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Kobe University Hospital

Kobe, Hyōgo, Japan

Saitama Cancer Center

Kitaadachi-gun, Saitama, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, South Korea

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, South Korea

Chi Mei Medical Center

Taikang, Tainan, Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Royal Marsden NHS Trust (Surrey)

Sutton, Surrey, United Kingdom

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, West Midlands, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

The Royal Marsden NHS Foundation Trust | The Royal Marden Hospital - The Royal Marsden Clinical Trials Unit (CTU)

London, , United Kingdom

Countries

United States; Belgium; France; Italy; Japan; South Korea; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.bayer.com/study/21136

Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.

https://www.clinicaltrialsregister.eu/ctr-search/search?query=21136

Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Other Identifiers

2020-003359-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

21136

Identifier Type: -

Identifier Source: org_study_id