Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer

NCT03482102 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-517
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of drugs as a possible treatment for Hepatocellular Carcinoma or Biliary Tract Cancer. The interventions involved in this study are:

• Durvalumab
• Tremelimumab
• Radiation Therapy

Conditions

Hepatocellular Carcinoma; Biliary Tract Cancer

Keywords

Hepatocellular Carcinoma; Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Best Overall Response rate

  The number of participants that achieve either a complete response or partial response. Response rate (ORR) is assessed using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors). Response is evaluated with the use of computed tomography (CT) and magnetic resonance imaging (MRI) scans. Participants are evaluated for response for the duration of treatment.Treatment continues until disease progression, treatment is considered a safety risk, physicians decision, withdrawal from the study, or until the participant is lost to follow up. The best overall response recorded for each participant is reported. * Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm (the sum may not be "0" if there are target nodes) * Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

  Start of cycle 3, start of cycle 5, and then the start of every subsequent cycle for the remainder of treatment. One cycle is 4 weeks. (approximately 3 years)

Secondary Outcomes (6)

• Number of Participants With Treatment Related Adverse Events

  From the start of treatment until 30 days after the last dose of study drug is received (approximately 5 years)

• Overall Survival

  From the start of treatment until the time of death or loss to follow-up (approximately 7 years)

• Disease Control Rate

  Screening, start of cycle 3, start of cycle 5, and then the start of every subsequent 4-week cycle for the remainder of treatment (approximately 3 years)

• Progression Free Survival

  From the start of treatment until the time of death or loss to follow-up, whichever occurs first (approximately 7 years)

• Duration of Response

  From first documentation of response to treatment until the time of disease progression (approximately 2 years)

Study Arms (1)

Tremelimumab + Durvalumab + Radiation

EXPERIMENTAL

* Durvalumab via IV infusion every 28 days for up to 4 doses/cycles * Tremelimumab via IV infusion every 28 days for up to 4 doses/cycles, and then continue durvalumab monotherapy every 4 weeks starting on Week 16 for up to 8 months. * Radiation therapy will only be given during cycle 2

Drug: Tremelimumab; Drug: Durvalumab; Radiation: Radiation

Interventions

Tremelimumab DRUG

Tremelimumab target the cancerous proteins and stop the cancer cells from suppressing the immune system

Tremelimumab + Durvalumab + Radiation

Durvalumab DRUG

Durvalumab target the cancerous proteins and stop the cancer cells from suppressing the immune system

Also known as: Imfinzi

Tremelimumab + Durvalumab + Radiation

Radiation RADIATION

Radiation therapy is used to shrink cancer cells.

Tremelimumab + Durvalumab + Radiation

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed hepatocellular carcinoma or biliary tract cancer
• Locally advanced/unresectable or metastatic disease
• Age ≥ 18 years at time of study entry
• ECOG Performance Status ≤ 1
• One previously unirradiated lesion amenable to 8 Gy x 3 radiotherapy based on dosimetric organ tolerance AND another unirradiated measurable lesion (per irRECIST) outside of the radiation field
• Immunotherapy-naïve
• Progressed on, be intolerant of, or refused sorafenib \[for HCC\], second line treatment and beyond for cholangiocarcinoma or gemcitabine-based chemotherapy for biliary tract cancer
• The benefits of sorafenib have been discussed with the patient and the patient has refused treatment with sorafenib.
• Viral status (Hepatitis B and C) must be known. All HBV-positive patients must be on antiviral medication for viral suppression.
• Patients with concomitant HBV infection must have a confirmed diagnosis of HBV characterized by the presence of hepatitis B core antibodies, and be sufficiently suppressed with active antiviral treatment (per local institutional practice) prior to enrollment to ensure adequate viral suppression (HBV deoxyribonucleic acid \[DNA\] \<2000 IU/mL).
• Patients with concomitant HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV ribonucleic acid (RNA or anti-HCV antibody upon enrollment.
• Body weight ≥ 30 kg
• Child-Pugh Score of A. A score of B7 is allowed without severe ascites or without hepatic encephalopathy.
• Adequate organ and marrow function, defined as:
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Prior irradiation to the planned radiation target lesion
• Prior immunotherapy including but not limited to anti-CTLA4, including tremelimumab anti-PD-1, and anti-PD-L1, including durvalumab
• Concurrent enrollment in another study unless it is an observational (e.g. non-interventional) study
• Received live attenuated vaccines within 30 days of first dose
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms using Fredericia's Correction
• History of primary immunodeficiency
• History of solid organ transplantation
• Active or prior documented autoimmune disease within the past 2 years (NOTE: The following are exceptions to this criterion: Participants with vitiligo or alopecia; Participants with hypothyroidism (e.g. following Hashimoto syndrome) who are stable on hormone replacement; Participants with celiac disease controlled by diet alone: Participants with Grave's disease, or any chronic skin condition not requiring systemic treatment. Participants without active disease in the last 5 years may be included but only after consultation with the study physician.)
• Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
• Prior other malignancy within 2 years (except for in situ disease, which is permissible)
• History of hypersensitivity to durvalumab, tremelimumab or any excipient
• History of (non-infectious) pneumonitis that required steroids; or evidence of interstitial lung disease or active, non-infectious pneumonitis
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Current or prior use of immunosuppressive medication within 28 days before the first dose of treatment on this protocol, with the exceptions of

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• AstraZeneca: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Biliary Tract Neoplasms

Interventions

tremelimumab; durvalumab; Radiation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Julie Koenig, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 29, 2018
• Study Start: May 14, 2018
• Primary Completion: February 28, 2024
• Study Completion: April 30, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)