Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)

Study Overview
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Brief Summary
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The proposed study is an open-label, single institution, single arm phase 1b study of neoadjuvant cabozantinib plus nivolumab in patients with locally advanced HCC.

Official Title
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Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)

Conditions
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Locally Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Cabozantinib
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have locally advanced/borderline resectable hepatocellular carcinoma. Must have measurable disease. Age ≥18 years. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients must have adequate organ and marrow function defined by study-specified laboratory tests. Patients must have adequate liver remnant and function. Antiviral therapy per local standard of care for hepatitis B. Woman of child bearing potential must have a negative pregnancy test. Must use acceptable form of birth control while on study. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: Fibrolamellar carcinoma or mixed HCC. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 6 months prior to trial registration. Concomitant Anticoagulation therapy. Any GI or pulmonary risks of bleeding. History of HIV Infection. Active co-infection with hepatitis B and hepatitis C. Active co-infection with hepatitis B and hepatitis D. Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy. History of any autoimmune disease requiring systemic treatment within the past 2 years. Any patient bearing an allograft is not eligible. Any additional malignancies with treatment or life-limiting cancers. Superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy would not exclude participation in this trial. Uncontrolled intercurrent illness. Corrected QT interval calculated by the Fridericia formula. Uncontrolled high blood pressure. Are pregnant or breastfeeding. Any gastrointestinal (GI) disorders. Any certain study-specified heart conditions 6 months prior to enrollment. Major surgery within 2 months before enrollment. Have any evidence of moderate or severe ascites. Any untreated or incompletely treated varices with bleeding or high-risk bleeding. Inability to swallow intact tablets. Known or suspected hypersensitivity to study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Cabozantinib<br>* Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.<br>* Other names: XL184;Drug: Nivolumab<br>* Nivolumab 240mg intravenously every 2 weeks (days 14, 28, 42, and 56 for a total of four doses), in combination with Cabozantinib 40mg by mouth daily for 8 weeks.<br>* Other names: OPDIVO, BMS 936558, MDX-1106, ONO-4538;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab. |  | 4 years | 
| Number of patients who complete pre-op treatment and proceed to surgery. |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who obtain R0 resection. |  | 4 years | 
| Percentage of participants who obtain a pathologic complete response (CR). |  | 4 years | 
| Percentage of participants who obtain a major pathologic responses (MPR) |  | 4 years | 
| Objective response rate (ORR) |  | 4 years | 
| Median Overall Survival (OS) |  | 5 years | 
| Disease free survival (DFS) |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Nivolumab, Cabozantinib, Neoadjuvant, Immunotherapy, Liver Cancer, Borderline Resectable, Advance Resectable, Neoplasms, Hepatocellular Carcinoma, Resection