Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma

NCT03937830 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 19009419-C-0094
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Most people with advanced HCC survive an average of 6 to 9 months. Researchers are evaluating a combination of treatment drugs to delay the progression of HCC; aiming to help people with HCC live longer. Objective: To study the 6-month progression-free survival in people with advanced HCC treated with bevacizumab, durvalumab, and TACE. Eligibility: Adults ages 18 and older with intermediate or advanced HCC Design: Participants will be screened with a physical exam and medical history. They will have tests to evaluate their hearts as well as blood and urine. A CT and/or MRI scans will be done during the study. If a prior tumor sample is not available; participants may undergo a biopsy. They may undergo an endoscopy of their esophagus and stomach. Participants will get the study drugs in 21-day cycles: Two treatment drugs will be injected into a vein every 3 weeks. Patients will have an interventional treatment procedure done by interventional radiology under sedation; chemotherapy beads will be infused into artery branches in the liver. Participants may have to stay in the hospital for 24 hours for observation, after this procedure. This interventional procedure may be done more than once during the study. Participants may need to repeat some of the screening tests throughout the study. Participants may have to stop taking some of their cancer treatment drugs during the study. Participants will continue on the study until their cancer progresses or until the side effects of the treatment drugs are not tolerable.

Conditions

Hepatocellular Cancer; Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma

Keywords

Immune Checkpoint Blockade; Combined Treatment; Immunotherapy; Anti-Tumor Immunity; Inhibition of the Blood Vessels Surrounding a Tumor

Outcome Measures

Primary Outcomes (2)

• To evaluate the 6-month progression free survival (PFS) in participants with advanced HCC BCLC stage B treated with bevacizumab, durvalumab, tremelimumab and TACE

  Proportion of participants with advanced HCC BCLC stage B that have progressive disease after 6 months

  6 months

• To evaluate the 6-month PFS in participants with BTC and HCC BCLC stage C treated with bevacizumab, durvalumab and tremelimumab

  Proportion of participants with BTC and HCC BCLC stage C that have progressive disease after 6 months

  6 months

Secondary Outcomes (4)

• To determine the best overall response (BOR) rate according to Response Evaluation Criteria (RECIST 1.1) in patients with advanced HCC and BTC

  every 9 weeks

• To characterize overall survival (OS) in patients with advanced HCC and BTC treated on this study

  death

• To determine the safety and feasibility of bevacizumab, durvalumab, tremelimumab and TACE in patients with advanced HCC

  every visit to clinical center

• To determine the safety and feasibility of bevacizumab, durvalumab, tremelimumab in patients with advanced BTC

  every visit to clinical center

Study Arms (3)

1/Arm 1

EXPERIMENTAL

Durvalumab, bevacizumab and tremelimumab

Drug: durvalumab; Drug: bevacizumab; Drug: Tremelimumab

2/Arm 2

EXPERIMENTAL

Durvalumab, bevacizumab, tremelimumab and TACE

Drug: durvalumab; Drug: Doxorubicin-Eluting Beads; Procedure: TACE; Drug: bevacizumab; Drug: Tremelimumab

3/Arm 3

EXPERIMENTAL

Durvalumab, low-dose bevacizumab, and tremelimumab

Drug: durvalumab; Drug: bevacizumab; Drug: Tremelimumab

Interventions

durvalumab DRUG

1,150 mg flat dose every 21 days, starting on day 1 of cycle 1

1/Arm 1; 2/Arm 2; 3/Arm 3

Doxorubicin-Eluting Beads DRUG

used for TACE (only in patients with HCC BCLC stage B)

2/Arm 2

TACE PROCEDURE

TACE with Doxorubicin-Eluting Beads (only in patients with HCC BCLC stage B) on Cycle 2. More TACE can be done if clinically necessary.

2/Arm 2

bevacizumab DRUG

7.5 mg/kg dose every 21 days, starting on day 1 of cycle 2

1/Arm 1; 2/Arm 2; 3/Arm 3

Tremelimumab DRUG

300, 150 or 75 mg once on day 1 of cycle 1

1/Arm 1; 2/Arm 2; 3/Arm 3

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have
• histopathological confirmation of HCC (Cohorts 1 and 3)
• histopathological confirmation of BTC or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC (Cohort 2).
• Participants should have progressed on standard of care systemic therapy or been intolerant of or have refused standard treatment. Note: For participants enrolled in Cohort 3 (HCC, BCLC stage B), standard of care chemotherapy is not required prior to enrollment.
• Participants must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation
• Participants must have evaluable or measurable disease per RECIST 1.1
• Participants must have at least one lesion accessible for TACE (Cohort 3)
• Participants must have lesions accessible for biopsy and be willing to undergo pre- and posttreatment biopsies
• ECOG performance status of 0 to 1
• If liver cirrhosis is present, patient must have a Child-Pugh score \<7
• Subjects with HCC must have BCLC C (Cohort 1) or BCLC B (Cohort 3)
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,000/mcL
• platelets greater than or equal to 60,000/mcL
• total bilirubin:if cirrhosis present: Part of Child Pugh requirement-If no cirrhosis: bilirubin should be less than or equal to 2 XULN

You may not qualify if:

• Participants who have had standard-of-care anti-cancer therapy or therapy with investigational agents (e.g. chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigation agents) or large field radiotherapy within 4 weeks prior to treatment initiation.
• Major surgery within 6 weeks prior to treatment initiation. Minor procedures (e.g. port placement, endoscopy with intervention) within 2 weeks prior to treatment initiation.
• Active central nervous system metastases and/or carcinomatous meningitis. Particpants with known active brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses.
• Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication (inhaled and topical steroids are permitted).
• Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID).
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg), based on an average of 3 BP readings on 2 sessions. Note: anti-hypertensive therapy to achieve these parameters is allowable.
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment
• Evidence of bleeding diathesis or significant coagulopathy (with or without current therapeutic anticoagulation).
• Recent (within 10 days of first dose of study treatment) use of aspirin
• Thromboembolic event within 6 months of initiation of study treatment (including cerebrovascular accident (CVA) and myocardial infarction (MI).
• History of hemoptysis (\>2.5 mL of bright red blood per episode) within 1 month prior to treatment initiation.
• Serious, non-healing wound, active ulcer, or untreated bone fracture.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

durvalumab; Bevacizumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 6, 2019
• Study Start: March 10, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-01-21

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)