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 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IIT-2020-RegoDurva
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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

Conditions

Advanced Biliary Tract Cancer

Keywords

Chemo-refractory

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment related adverse events

  CTCAE Version 5.0

  At the end of cycle 1 (each cycle is 28 days) until 30 days after end of treatment (EOT)

• Progressin Free Survival (PFS)

  RECIST Version 1.1

  At the end of each cycle (28 days) until disease progression or 2 years (end of study), whichever occurs first

Secondary Outcomes (4)

• Overall Response (OR)

  Start of treatment to EOT or 2 years (end of study), whichever occurs first

• Disease Control Rate (DCR)

  Start of treatment to EOT or 2 years (end of study), whichever occurs first

• Overall Response Rate (ORR)

  Start of treatment to EOT or 2 years (end of study), whichever occurs first

• Overall Survival (OS)

  Start of treatment to EOT or 2 years (end of study), whichever occurs first

Study Arms (1)

Dose Finding Regorafenib

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Regorafenib

Interventions

Durvalumab DRUG

Intra-Venous(IV) once every 28 days (approximately every 4 weeks \[q4w\])

Dose Finding Regorafenib

Regorafenib DRUG

Oral once per day, Days 1 - 21 every 28 days

Dose Finding Regorafenib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (5)

University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, 66210, United States

Location

The University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

The University of Kansas Medical Center

North Kansas City, Missouri, 64116, United States

Location

MeSH Terms

Interventions

durvalumab; regorafenib

Study Officials

• Raed Al-Rajabi, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, unblinded phase I/II study with safety dose-finding in Phase I followed by efficacy determination in Phase II if maximum tolerated dose (MTD) is found in Phase I.

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 4, 2021
• Study Start: March 22, 2022
• Primary Completion: November 12, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (5)