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

Phase 1

Completed

• Conditions: Locally Advanced Hepatocellular Carcinoma
• Interventions: Drug: Cabozantinib; Drug: Nivolumab

• Registration Number: NCT03299946
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-27
• Study First Submitted QC: 2017-09-27
• Study First Posted: 2017-10-03
• Study Start: 2018-05-14
• Primary Completion: 2019-12-09
• Study Completion: 2021-10-01
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-24
• Last Update Posted: 2023-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Must have locally advanced/borderline resectable hepatocellular carcinoma.
2. Must have measurable disease.
3. Age ≥18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
5. Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
6. Patients must have adequate liver remnant and function.
7. Antiviral therapy per local standard of care for hepatitis B.
8. Woman of child bearing potential must have a negative pregnancy test.
9. Must use acceptable form of birth control while on study.
10. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

1. Fibrolamellar carcinoma or mixed HCC.
2. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 6 months prior to trial registration.
3. Concomitant Anticoagulation therapy.
4. Any GI or pulmonary risks of bleeding.
5. History of HIV Infection.
6. Active co-infection with hepatitis B and hepatitis C.
7. Active co-infection with hepatitis B and hepatitis D.
8. Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.
9. History of any autoimmune disease requiring systemic treatment within the past 2 years. Any patient bearing an allograft is not eligible.
10. 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.
11. Uncontrolled intercurrent illness.
12. Corrected QT interval calculated by the Fridericia formula.
13. Uncontrolled high blood pressure.
14. Are pregnant or breastfeeding.
15. Any gastrointestinal (GI) disorders.
16. Any certain study-specified heart conditions 6 months prior to enrollment.
17. Major surgery within 2 months before enrollment.
18. Have any evidence of moderate or severe ascites.
19. Any untreated or incompletely treated varices with bleeding or high-risk bleeding.
20. Inability to swallow intact tablets.
21. Known or suspected hypersensitivity to study treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	Cabozantinib	-
Arm 1	Nivolumab	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Median Overall Survival (OS)	5 years
Objective response rate (ORR)	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
Disease free survival (DFS)	5 years
Percentage of participants who obtain R0 resection.	4 years

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center; 🇺🇸 Baltimore, Maryland, United States