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

March 24, 2023 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Drug: Cabozantinib
Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.
Other Names:
  • XL184
Drug: Nivolumab
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.
Other Names:
  • OPDIVO, BMS 936558, MDX-1106, ONO-4538

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Bristol-Myers Squibb
Exelixis

Investigators

  • Principal Investigator: Daniel Laheru, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2018

Primary Completion (Actual)

December 9, 2019

Study Completion (Actual)

October 1, 2021

Study Registration Dates

First Submitted

September 27, 2017

First Submitted That Met QC Criteria

September 27, 2017

First Posted (Actual)

October 3, 2017

Study Record Updates

Last Update Posted (Actual)

March 28, 2023

Last Update Submitted That Met QC Criteria

March 24, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J17136
  • IRB00149350 (Other Identifier: Johns Hopkins University)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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