Clinical Trials /

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

NCT04781192

Description:

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

Related Conditions:
  • Cholangiocarcinoma
  • Gallbladder Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: IIT-2020-RegoDurva
  • NCT ID: NCT04781192

Conditions

  • Advanced Biliary Tract Cancer

Interventions

DrugSynonymsArms
DurvalumabDose Finding Regorafenib
RegorafenibDose Finding Regorafenib

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Dose Finding RegorafenibExperimentalWe 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
  • Durvalumab
  • Regorafenib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment related adverse events
Time Frame:At the end of cycle 1 (each cycle is 28 days) until 30 days after end of treatment (EOT)
Safety Issue:
Description:CTCAE Version 5.0

Secondary Outcome Measures

Measure:Overall Response (OR)
Time Frame:Start of treatment to EOT or 2 years (end of study), whichever occurs first
Safety Issue:
Description:RECIST Version 1.1
Measure:Disease Control Rate (DCR)
Time Frame:Start of treatment to EOT or 2 years (end of study), whichever occurs first
Safety Issue:
Description:RECIST Version 1.1
Measure:Overall Response Rate (ORR)
Time Frame:Start of treatment to EOT or 2 years (end of study), whichever occurs first
Safety Issue:
Description:RECIST Version 1.1
Measure:Overall Survival (OS)
Time Frame:Start of treatment to EOT or 2 years (end of study), whichever occurs first
Safety Issue:
Description:RECIST Version 1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Kansas Medical Center

Trial Keywords

  • Chemo-refractory

Last Updated

March 4, 2021