The Purpose of This Trial is to Determine if Regorafenib Plus Durvalumab (MEDI4736) is Safe and Effective in Treatment of Chemo Refractory Advanced Biliary Tract Cancers

Learn more about:
Related Clinical Trial
Study of Combination Therapy of D07001-Softgel Capsules and Xeloda/TS-1 in Subjects With Advanced Biliary Tract Cancer Phase Ib/II Single-arm Study of mFOLFOX6, Bevacizumab and Atezolizumab in Advanced Biliary Tract Cancer A Safety and Efficacy Study of Surufatinib Combination With Toripalimab in Patients With Recurrent Biliary Tract Cancer Metabolic Stress-induced Exercise to Prevent Loss of Muscle Mass in Patients With Pancreatic and Biliary Tract Cancer The Registry of Genetic Alterations of Taiwan Biliary Tract Cancer A Study of ABL001 in Combination With Irinotecan or Paclitaxel in Patients With Advanced or Metastatic Solid Tumors Prognostic and Predictive Markers of Response to Treatment in Patients With Bile Duct Cancer: ACABi PRONOBIL Study Quality of Life of Patients Over 75 Yars Undergoing Palliative Chemotherapy Predicting Disease Progression and/or Recurrence in Cancer Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab Endoluminal Radiofrequency Ablation for the Treatment of Malignant Biliary Stenosis A Phase 1/2 Study of SC-43 in Combination With Cisplatin The Purpose of This Trial is to Determine if Regorafenib Plus Durvalumab (MEDI4736) is Safe and Effective in Treatment of Chemo Refractory Advanced Biliary Tract Cancers Phase II Study of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Biliary Tract Cancer Camrelizumab Combined With Apatinib and Capecitabine in Patients With Advanced Unresectable Biliary Tract Cancer. A Study of Atezolizumab With or Without Bevacizumab in Combination With Cisplatin Plus Gemcitabine in Patients With Untreated, Advanced Biliary Tract Cancer A Phase II Study for Nab-paclitaxel Plus Cisplatin vs Gemcitabine Plus Cispatin as First Line Chemotherapy in Advanced Biliary Tract Cancer A Study of HA121-28 Tablets in Advanced Biliary Tract Cancer A Clinical Study of PD-L1 Antibody ZKAB001 Combined With Capecitabine in Resected Biliary Tract Cancer A Trial of SHR1258 in Patients With Biliary Tract Cancer Perception Prognosis, Goals of Treatment, and Communication IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread A Study to Assess the Safety, Tolerability and Anti-tumour Activity of Ascending Doses of Selumetinib in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours Adjuvant Capecitabine vs Gemcitabine Plus Cisplatin in Resected Extrahepatic Cholangiocarcinoma My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors Tremelimumab With Chemoembolization or Ablation for Liver Cancer Preoperative Nutritional Support in Malnutritional Cancer Patients Multibending vs Conventional Endoscope for Direct Peroral Cholangioscopy Surgical Outcomes Database For Faculty of Hepatopancreatic Biliary Surgery SOX Sequential S-1 in Advanced Biliary Tract Carcinoma(BTC)and Pancreatic Cancer Effect of Early Management on PAin and DEpression in Patients With PancreatoBiliary Cancer, EPADE-PB Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) in Previously Treated Participants With Select Solid Tumors (MK-7902-005/E7080-G000-224/LEAP-005) Surgery Plus Celiac Nerve Block for Long-term Pancreatic Cancer Pain Control Covered Versus Uncovered SEMS for Palliation of Malignant Biliary Strictures. Parenteral Nutrition in Patients With Biliopancreatic Mass Lesions Early Palliative Care on Quality of Life of Advanced Cancer Patients Patient Activation Through Counseling, Exercise and Mobilization Extracellular RNA Markers of Liver Disease and Cancer X-MAS Biliary Study With Covered Biliary Stent A Randomized, Open-Label, Comparative, Parallel-Group, Multicenter Study of SPARC1507 Anti-HER2 Therapy in Patients of HER2 Positive Metastatic Carcinoma of Digestive System The Efficacy and Safety of Nab-paclitaxel Plus S-1 in First-line Treatment of Advanced Biliary Tract Adenocarcinoma XELOX in Advanced Biliary Tract Carcinoma After Failure of Gemcitabine-based Chemotherapy Phase II Study of Refametinib, a MEK Inhibitor, as Second-line Treatment in Advanced Biliary Tract Adenocarcinoma Study of Gemcitabine, Irinotecan and Panitumumab in Patients With Advanced and Metastatic Biliary Tract Adenocarcinoma A Trial Evaluating Surufatinib Efficacy and Safety in Biliary Tract Carcinoma Patients Study of Surufatinib as Second-line Treatment in Patients With Biliary Tract Carcinoma A Study of FOLFOX6 With Bevacizumab for Biliary System Carcinoma Combination of Targeted and Immunotherapy for Advanced Biliary Tract and Esophagogastric Gastric Cancer A Study of AbGn-107 in Patients With Gastric, Colorectal, Pancreatic or Biliary Cancer Gemcitabine and Capecitabine to Treat Patients With Advanced Pancreatic and Biliary Cancers A Prospective Cohort Study of Patients With Hepatobiliary Cancer Treated With Immune Checkpoint Inhibitors GTX Regimen for Biliary Cancers Phase II Study of Gemcitabine and TS-1 in Biliary Trat Cancer A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases A Phase I/II Study of the Pan-immunotherapy in Patients With Local Advanced/Metastatic BTC Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic BTC Phase II Study of SPI-1620 in Combination With Docetaxel as a Second-Line to Treat Biliary Cancer FOLFIRINOX for 2nd-line Treatment of BTC Study of PD-1 Inhibitor in Combination With Gemcitabine/Cisplatin for Advancer BTCs FOLFIRI as Salvage Treatment in Metastatic Biliary Tract Cancer (BTC) Patients Who Were Failed After Gemcitabine Containing Chemotherapy: A Phase II Single Arm Prospective Study Pemetrexed in Combination With Erlotinib as a Salvage Treatment in Patients With Metastatic Biliary Tract Cancer (BTC) Who Failed Gemcitabine Containing Chemotherapy: A Phase II Single Arm Prospective Study Irinotecan, Gemcitabine, Chemotherapy for Biliary Tract Cancer Rucaparib in Combination With Nivolumab in Patients With Advanced or Metastatic Biliary Tract Cancer Following Platinum Therapy Study of Pembrolizumab in Metastatic Biliary Tract Cancer as Second-line Treatment After Failing to at Least One Cytotoxic Chemotherapy Regimen: Integration of Genomic Analysis to Identify Predictive Molecular Subtypes A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers Phase I Study of Gemcitabine or S-1 Adjuvant Therapy After Hemihepatectomy for Biliary Tract Cancer Gemcitabine/Cisplatin/S-1(GCS) Combination Therapy for Patients With Advanced Biliary Tract Cancer Phase II Study of Gemcitabine Versus S-1 Adjuvant Therapy After Hemihepatectomy for Biliary Tract Cancer Docetaxel and Oxaliplatin Combination With Locally Advanced or Metastatic Biliary Tract Cancer A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer Study of S-1 Oxaliplatin (SOX) for Biliary Tract Cancer (BTC) (Ampullary Adenocarcinoma) Trastuzumab in HER2-positive Biliary Tract Cancer Study of Lenvatinib (E7080) in Unresectable Biliary Tract Cancer Who Failed Gemcitabine-based Combination Chemotherapy Study of D07001-Softgel Capsules in Subjects With Gastrointestinal Cancer in Dose-Escalation Phase and in Subjects With Biliary Tract Cancer in Dose-Expansion Phase Second Line Therapy in Advanced Biliary Tract Cancer Phase II Study of FOLFOXIRI in Patients With Locally Advanced or Metastatic Biliary Tract Cancer GAMBIT Trial: Cisplatin Plus Irinotecan in the Treatment of Gallbladder or Biliary Tract Cancer Study of TH-302 Monotherapy as Second-line Treatment in Advanced Biliary Tract Cancer Trial of Infusional FOLFIRINOX in First Line Treatment of Advanced Biliary Tract Cancers Phase Ib/II Trial of Nal-Irinotecan and Nivolumab as Second-Line Treatment in Patients With Advanced Biliary Tract Cancer Anlotinib in Combination With PD1 With Gemcitabine Plus(+)Cisplatin for Unresectable or Metastatic Biliary Tract Cancer Gemcitabine+ Capecitabine Vs Capecitabine in Curatively Resected Biliary Tract Cancer Randomized Phase 2 Study With Gemcitabine Alone and Combination Therapy for Patients With Advanced Biliary Tract Cancer A Study of Selective HDAC6 Inhibition With KA2507 in Advanced Biliary Tract Cancer Varlitinib Plus Capecitabine in Chinese Patients With Advanced or Metastatic Biliary Tract Cancer Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer Oral Rehydration Therapy for Short Hydration in Chemotherapy With CDDP Plus GEM for Biliary Tract Cancer A Study of RC48 in Subjects With HER2 Overexpressed Metastatic Biliary Tract Cancer. Case Series Study of Biliary Tract Cancer Patients in Japan GEM/Cisplatin/S-1 vs GEM/Cisplatin for Biliary Tract Cancer Molecular Profiling of Advanced Biliary Tract Cancers MEK162 in Combination With Capecitabine in Advanced Biliary Tract Cancer Allogeneic NK Cell (“SMT-NK”) in Combination With Pembrolizumab in Advanced Biliary Tract Cancer Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer Toripalimab Combined With S1 and Albumin Paclitaxel in Patients With Advanced Biliary Tract Cancer Vessel Resection and Reconstruction of Biliary Tract Cancers Apatinib as Second Line Therapy in Patients With Advanced Refractory Biliary Tract Cancers A Phase I Study of Adjuvant Chemotherapy With GS in Biliary Tract Cancer Undergoing Resection Without Major Hepatectomy A Phase II Trial of Preoperative Chemotherapy for Biliary Tract Cancer (BTC) With Node Metastasis A Phase I Study of Adjuvant Chemotherapy With GC in Biliary Tract Cancer Undergoing Resection Without Major Hepatectomy Study of Nivolumab in Patients With Advanced Refractory Biliary Tract Cancers Study of the Combination of DKN-01 and Nivolumab in Previously Treated Patients With Advanced Biliary Tract Cancer (BTC) NGS as the First-line Treatment in Advanced Biliary Tract Cancer Identification of Prognostic Gene Mutations in Biliary Tract Cancer Using Whole Genome Sequencing NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer Molecular Profiling of Advanced Biliary Tract Cancers

Brief Title

The Purpose of This Trial is to Determine if Regorafenib Plus Durvalumab (MEDI4736) is Safe and Effective in Treatment of Chemo Refractory Advanced Biliary Tract Cancers

Official Title

Phase I/II Clinical Trial of Regorafenib Plus Durvalumab (MEDI4736) in Patients With Chemo Refractory Advanced Biliary Tract Cancers

Brief Summary

      The purpose of this study is to measure how effective combining Durvalumab and Regorafenib
      will be for participants with advance stage biliary track carcinoma who have received one
      line of prior treatment
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Incidence of treatment related adverse events

Secondary Outcome

 Overall Response (OR)

Condition

Advanced Biliary Tract Cancer

Intervention

Durvalumab

Study Arms / Comparison Groups

 Dose Finding Regorafenib
Description:  We will use a 3 + 3 design with two dose levels of 80 mg and 120 mg to discover the Maximum Tolerated Dose (MTD) for regorafenib

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

40

Start Date

October 2021

Completion Date

December 2023

Primary Completion Date

November 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Ability of patient OR Legally Authorized Representative (LAR) to understand this
             study, and participant or LAR willingness to sign a written informed consent

          -  Can swallow tablets and self-administer medication

          -  Progressed on at least one line of therapy (no restrictions on type of previous
             treatment)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status = 0 - 1

          -  Measurable disease with at least 1 lesion that qualifies as a RECIST 1.1 Target Lesion
             (TL) at baseline. Previously irradiated lesion cannot be considered as Target Lesion
             (TL) except in cases of documented progression of the lesion since the completion of
             radiation therapy

          -  Histologically confirmed unresectable or metastatic intrahepatic/extrahepatic
             cholangiocarcinoma or gallbladder cancer with radiographic progression, who have
             progressed on one line of therapy / failed adjuvant therapy

          -  Life expectancy of at least 3 months

          -  Recovery to baseline or < Grade 2 CTCAE v5.0 from toxicities related to any prior
             treatments, unless adverse event's (AE(s)) are clinically nonsignificant and/or stable
             on supportive therapy

          -  Adequate organ function per laboratory results

          -  Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin
             and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) will be allowed
             provided that no prior evidence of underlying abnormality in coagulation parameters
             exists. Close monitoring of at least weekly evaluations will be performed until
             international normalized ratio/ partial thromboplastin time (INR/PTT) is stable based
             on a measurement that is pre-dose as defined by the local standard of care

          -  Weight > 30 kg (66 lbs)

          -  Women of child-bearing potential and men with partners of child-bearing potential must
             agree to use an acceptable form of contraception for the duration of study
             participation, and for 7 months after the last study treatment

          -  Men of child-bearing potential must agree not to donate sperm while on this study and
             for 180 days (6 months) after the last dose of study treatment

        Exclusion Criteria:

          -  Current or anticipated use of other investigational agents while participating in
             another clinical study, unless it is an observational (noninterventional) clinical
             study or during the follow-up period of an interventional study

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Pregnant or breastfeeding

          -  Ampullary carcinoma

          -  Previous treatment with regorafenib

          -  Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1,
             including durvalumab), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
             inhibitors, or agent directed to another co-inhibitory T cell receptor

          -  Previous treatment with live vaccine within 30 days of planned start of study drugs
             (seasonal flu vaccines that do not contain a live virus are permitted)

          -  Active autoimmune disease (active defined as having autoimmune disease related
             symptoms and detectable autoantibodies) that has required systemic treatment in the
             past 2 years

          -  Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of study
             drugs. Except Intranasal, inhaled, topical steroids, or local steroid injections
             (e.g., intra articular injection), systemic corticosteroids at physiologic doses not
             to exceed 10 mg/day of prednisone or its equivalent, steroids as premedication for
             hypersensitivity reactions (e.g., CT scan premedication)

          -  Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies).
             Dual active hepatitis B virus (HBV) infection (HBsAg (+) and /or detectable HBV DNA)
             and HCV infection (anti-HCV Ab(+) and detectable HCV RNA) at study entry. Single
             active infection of HBV or HCV infection is allowed with treatment by local standards

          -  Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
             identified either on the baseline brain imaging, unless known and treated with stable
             for >4 weeks

          -  Significant acute gastrointestinal disorders with diarrhea as a major symptom e.g.,
             Crohn's disease, malabsorption, or CTCAE Grade ≥ 2 diarrhea of any etiology

          -  Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine
             therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
             antibodies) ≤ 21 days prior to the first dose of study drug

          -  Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal
             therapy for cancer treatment. Concurrent use of hormonal therapy for
             non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
             However, the palliative radiation to non-targeted lesions is allowed

          -  Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
             within 8 weeks before first dose. Note: Complete healing of an intra-abdominal abscess
             must be confirmed before first dose

          -  Uncontrollable ascites or pleural effusion

          -  Clinically significant gross hematuria, hematemesis, or hemoptysis of >0.5 tsp (2.5ml)
             of red blood, or other history of grade 3 significant bleeding within 8 weeks

          -  Any unresolved toxicity NCI CTCAE v 5.0 Grade ≥2 from previous anticancer therapy with
             the exception of neuropathy grade 2 and below, alopecia, vitiligo, and the laboratory
             values defined in the inclusion criteria

          -  Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks
             before first dose of study treatment. Complete wound healing from major surgery must
             have occurred 1 month before first dose and from minor surgery (e.g., simple excision,
             tooth extraction) at least 10 days before first dose. Patients with clinically
             relevant ongoing complications from prior surgery are not eligible

          -  History of organ transplantation

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, interstitial lung disease

          -  Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg
             systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment

          -  Mean QT interval corrected for heart rate (QTcF) >470 ms calculated from 3
             electrocardiograms (ECGs) (within 15 minutes at 5 minutes apart) using Fridericia's
             Correction

          -  Stroke (including transient ischemic attack transient ischemic attack (TIA),
             myocardial infarction (MI), or other ischemic event, or acute thromboembolic event
             (e.g., deep venous thrombosis, pulmonary embolism) that are NOT asymptomatic with
             local standard anti-coagulation within 4 weeks before first dose

          -  History of another primary malignancy in the last 3 years except:

               -  Malignancy treated with curative intent and with no known active disease ≥3 years
                  before the first dose of IP and of low potential risk for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

          -  Use of any Herbal remedy

          -  Ongoing infection >grade 2

          -  Known allergy or hypersensitivity to any of the study drugs

          -  Proteinuria > Grade3 (>3.5g/24 hours)

          -  Active infection with tuberculosis (TB) (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and TB testing in line with
             local practice)

          -  Participants with HBV infection (as characterized by positive hepatitis B surface
             antigen [HBsAg] and/or anti-hepatitis B core antibodies (anti-HBc) with detectable HBV
             deoxyribonucleic acid (DNA) [≥10 international units (IU)/mL or above the limit of
             detection per local laboratory]) must receive antiviral therapy prior to randomization
             to ensure adequate viral suppression

          -  Participants must remain on antiviral therapy for the study duration and for 6 months
             after the last dose of study treatment. Participants who test positive for anti-HBc
             with undetectable HBV DNA (<10 IU/mL or under the limit of detection per local
             laboratory) do not require antiviral therapy unless HBV DNA exceeds 10IU/mL or reaches
             detectable limits per local laboratory during the course of treatment

          -  Patients positive for hepatitis C (HCV) antibody. EXCEPTIONS: Patients positive for
             hepatitis C (HCV) are eligible only if polymerase chain reaction is negative for HCV
             RNA.

        Patients positive for hepatitis C (HCV) are eligible if they undergo treatment per local
        guidelines
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Raed Al-Rajabi, MD, 913-588-3671, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04781192

Organization ID

IIT-2020-RegoDurva


Responsible Party

Sponsor

Study Sponsor

University of Kansas Medical Center


Study Sponsor

Raed Al-Rajabi, MD, Principal Investigator, University of Kansas Medical Center


Verification Date

February 2021