Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma
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ClinicalTrials.gov Identifier: NCT03937830 |
Recruitment Status :
Recruiting
First Posted : May 6, 2019
Last Update Posted : May 16, 2024
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Tracking Information | |||||||||||||||
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First Submitted Date ICMJE | May 3, 2019 | ||||||||||||||
First Posted Date ICMJE | May 6, 2019 | ||||||||||||||
Last Update Posted Date | May 16, 2024 | ||||||||||||||
Actual Study Start Date ICMJE | March 10, 2021 | ||||||||||||||
Estimated Primary Completion Date | December 31, 2025 (Final data collection date for primary outcome measure) | ||||||||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
To evaluate 6-month progression free survival (PFS [ Time Frame: 6 months ] Proportion of patients that have progressive disease after 6 months
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Change History | |||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||
Descriptive Information | |||||||||||||||
Brief Title ICMJE | Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma | ||||||||||||||
Official Title ICMJE | A Phase II Study of Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinoma (BTC) | ||||||||||||||
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. |
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Detailed Description | Background: Worldwide, hepatocellular carcinoma (HCC) is the fourth most common cause of cancer related death with a median survival of 6-9 months. Biliary tract carcinoma (BTC) is relatively uncommon and includes cancers of the gallbladder and intra- and extra-hepatic biliary ductal system, although periampullary tumors are often considered part of this group as well. A class of agents that in the recent years has been at the epicenter of immunotherapy approaches in gastrointestinal malignancies are the monoclonal antibodies (mAbs) against the immune checkpoint inhibitors CTLA4, PD-1 and PD-L1. Durvalumab is a human monoclonal antibody of the immunoglobulin G1 kappa (IgG1k ) subclass. Durvalumab inhibits binding of programmed cell death ligand 1 (PD-L1) to programmed cell death 1 (PD-1) and CD80. Anti-PD-L1 antibodies directly target tumor cells and are expected to have less adverse events in comparison with anti-PD-1 antibodies that target effector T-cells in the tumor microenvironment. Tremelimumab is a human IgG2 mAb directed against CTLA-4. Tremelimumab blocks the inhibitory effect of CTLA-4, and therefore enhances T cell activation. Angiogenesis is defined as the formation of new blood capillaries, which is a complex process that promotes vascular endothelial growth factor (VEGF) and other proangiogenic factor expression, thus enhancing metastasis. Inhibition of VEGF function by bevacizumab can lead to the inhibition of the new blood vessels formation surrounding a tumor, and consequently arrest the tumor growth by depriving essential nutrients and oxygen. TACE has been shown to induce anti-tumor immunity. Early phase studies have shown that anti-VEGF treatment with bevacizumab in combination with TACE decreases neovascular formation. We have previously shown that locoregional therapies can be safely combined with immune checkpoint blockade. There are also preclinical data suggesting that anti-VEGF therapy may target myeloid cells with suppressor activity. Objectives: To evaluate the 6-month progression free survival (PFS) in patients with advanced HCC BCLC stage B treated with bevacizumab, durvalumab, tremelimumab and TACE. To evaluate the 6-month PFS in patients with BTC and HCC BCLC stage C treated with bevacizumab, durvalumab and tremelimumab. Eligibility: Histopathological confirmation of HCC or 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. Patients must have evaluable or measurable disease per RECIST 1.1. Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation. Design: This is an open label Phase II trial conducted to evaluate efficacy of durvalumab, bevacizumab and tremelimumab combined treatment in patients with advanced HCC BCLC stage C or BTC and efficacy of durvalumab, bevacizumab, tremelimumab and TACE combined treatment in patients with advanced HCC BCLC stage B. Initially 3-18 patients with HCC BCLC Stage C or BTC will be enrolled into safety run-in of Arm 1 to determine the safety of combined treatment of durvalumab, bevacizumab and tremelimumab. Once safety has been determined, subsequent patients with HCC BCLC Stage C and BTC will be enrolled in Arm 1 and patients with HCC BCLC Stage B will start enrollment into Arm 2, consistent of durvalumab, bevacizumab, tremelimumab and multiple TACE procedures. Treatment will continue until progression or unbearable toxicity. |
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Study Type ICMJE | Interventional | ||||||||||||||
Study Phase ICMJE | Phase 2 | ||||||||||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||
Recruitment Status ICMJE | Recruiting | ||||||||||||||
Estimated Enrollment ICMJE |
72 | ||||||||||||||
Original Estimated Enrollment ICMJE |
22 | ||||||||||||||
Estimated Study Completion Date ICMJE | December 31, 2025 | ||||||||||||||
Estimated Primary Completion Date | December 31, 2025 (Final data collection date for primary outcome measure) | ||||||||||||||
Eligibility Criteria ICMJE |
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EXCLUSION CRITERIA:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||||||||
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Administrative Information | |||||||||||||||
NCT Number ICMJE | NCT03937830 | ||||||||||||||
Other Study ID Numbers ICMJE | 190094 19-C-0094 |
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Has Data Monitoring Committee | Not Provided | ||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) | ||||||||||||||
Original Responsible Party | Same as current | ||||||||||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||||||||
Collaborators ICMJE | Not Provided | ||||||||||||||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | ||||||||||||||
Verification Date | March 25, 2024 | ||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |