Clinical Trials /

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

Description:

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.

Related Conditions:
  • Anaplastic Astrocytoma
  • Biliary Tract Carcinoma
  • Esophageal Squamous Cell Carcinoma
  • Glioblastoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial to Learn Whether Regorafenib in Combination With Nivolumab Can Improve Tumor Responses and How Safe it is for Participants With Solid Tumors
  • Official Title: A Multi-indication, Single-treatment Arm, Open-label Phase 2 Study of Regorafenib and Nivolumab in Combination in Patients With Recurrent or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 21136
  • SECONDARY ID: 2020-003359-13
  • NCT ID: NCT04704154

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
Regorafenib, (Stivarga, BAY73-4506)Regorafenib+Nivolumab
Nivolumab (Opdivo)Regorafenib+Nivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Regorafenib+NivolumabExperimentalParallel-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.
  • Regorafenib, (Stivarga, BAY73-4506)
  • Nivolumab (Opdivo)

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
             progressed on or after prior systemic therapy 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)
             mutations.

          -  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 150/90
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to the last participant having been followed for approximately 10 months, summing up to approximately 2.5 years
Safety Issue:
Description:Per Response evaluation criteria in solid tumors 1.1 (RECIST 1.1) by local assessment for all solid tumors except GBM/AA (Glioblastoma multiforme/Anaplastic astrocytoma) Per Response assessment in neuro-oncology (RANO) by local assessment for GBM/AA

Secondary Outcome Measures

Measure:Duration of response (DOR)
Time Frame:From first dosing up to the end of the study (LPLV), summing up to approximately 4 years
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:From first dosing up to the end of the study (LPLV), summing up to approximately 4 years
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:From first dosing up to the end of the study (LPLV), summing up to approximately 4 years
Safety Issue:
Description:
Measure:6 months PFS
Time Frame:6 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From first dosing up to the end of the study (LPLV), summing up to approximately 4 years
Safety Issue:
Description:
Measure:1 year OS
Time Frame:1 year
Safety Issue:
Description:
Measure:Severity of AEs (adverse events) per CTCAE v 5.0
Time Frame:From first dosing up to the end of the study (LPLV), summing up to approximately 4 years
Safety Issue:
Description:CTCAE: Common terminology criteria for adverse events
Measure:Number of participants with adverse events
Time Frame:From first dosing up to the end of the study (LPLV), summing up to approximately 4 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

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

Last Updated

January 11, 2021