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

NCT04704154 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 211362020-003359-13
• Study Type: interventional
• Target: 175
• Locations: 8 countries
• Sites: 34

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

Keywords

Pancreatic Ductal Adenocarcinoma (PDAC); Head and Neck Squamous Cell Carcinoma (HNSCC); Esophageal Squamous Cell Carcinoma (ESCC); Glioblastoma Multiforme (GBM); Anaplastic Astrocytoma (AA); Biliary Tract Carcinoma (BTC); PD-1 inhibitor; nivolumab; regorafenib; multi-kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Tumor response was evaluated as ORR per RECIST 1.1 by local assessments for all tumor types, except for GBM/AA, where ORR per RANO by local assessment was used. ORR was defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR). Participants for whom best overall tumor response was not CR or PR, as well as participants without any post-baseline tumor assessment were considered non-responders. Descriptive statistics were done, no inferential statistical analyses were performed.

  From first participant enrolled to cut-off date (ie after the last participant has been followed for approximately 10 months) approximately 26 months

Secondary Outcomes (7)

• Duration of Response (DOR)

  From first participant enrolled to cut-off date (ie after the last participant has been followed for approximately 10 months) approximately 26 months

• Disease Control Rate (DCR)

  From first participant enrolled to cut-off date (ie after the last participant has been followed for approximately 10 months) approximately 26 months

• Progression Free Survival (PFS)

  From first participant enrolled to cut-off date (ie after the last participant has been followed for approximately 10 months) approximately 26 months

• 6 Months PFS

  Up to last participant follow 6 months (approximately 22 months)

• Overall Survival (OS)

  From first participant enrolled to cut-off date (ie after the last participant has been followed for approximately 10 months) approximately 26 months

Study Arms (1)

Regorafenib+Nivolumab

EXPERIMENTAL

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.

Drug: Regorafenib, (Stivarga, BAY73-4506); Drug: Nivolumab (Opdivo)

Interventions

Regorafenib, (Stivarga, BAY73-4506) 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).

Regorafenib+Nivolumab

Nivolumab (Opdivo) DRUG

480 mg administered on Day 1 of each treatment cycle.

Regorafenib+Nivolumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead
• Bristol Myers Squibb Co. and Ono Pharmaceutical Co., Ltd: collaborator

Study Sites (34)

City of Hope - Duarte Cancer Center

Duarte, California, 91010, United States

Location

Rocky Mountain Cancer Centers / Aurora, CO

Aurora, Colorado, 80012, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

Baylor Charles A. Sammons Cancer Center at Dallas

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hôpital Erasme/Erasmus Ziekenhuis

Brussels, 1070, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

Institut Bergonie - Unicancer Nouvelle Aquitaine

Bordeaux, 33076, France

Location

UNICANCER - Centre Leon Berard (CLB)

Lyon, 69008, France

Location

APHP-Hopital la Pitie Salpetriere

Paris, 75651, France

Location

Institut de Cancerologie Ouest - Saint-Herblain

Saint-Herblain, 44800, France

Location

Institut Claudius Regaud - iUCT Oncopole

Toulouse, 31059, France

Location

Gustave Roussy - Departement Oncologie-Radiotherapie

Villejuif, 94805, France

Location

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

Bologna, Emilia-Romagna, 40139, Italy

Location

IRCCS Foundation Istituto Neurologico Carlo Besta

Milan, Lombardy, 20133, Italy

Location

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

Rozzano, Lombardy, 20089, Italy

Location

Istituto Oncologico Veneto_Padova - UOC Oncologia 1

Padua, Veneto, 35128, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - Oncologia Falck

Milan, 20162, Italy

Location

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Saitama Cancer Center

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

Location

Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 3080, South Korea

Location

Chi Mei Medical Center

Taikang, Tainan, 71004, Taiwan

Location

China Medical University Hospital

Taichung, 404327, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Royal Marsden NHS Trust (Surrey)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, West Midlands, CV2 2DX, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

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

London, SW3 6JJ, United Kingdom

Location

Related Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Glioblastoma; Astrocytoma

Interventions

regorafenib; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 11, 2021
• Study Start: February 3, 2021
• Primary Completion: March 9, 2023
• Study Completion: March 29, 2024
• Last Updated: April 18, 2025
• Results First Posted: July 23, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (3); KR (2); GB (4); BE (3); FR (6); US (6); JP (5); IT (5)