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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)

Primary Purpose

Locally Advanced Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cabozantinib
Nivolumab
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Hepatocellular Carcinoma focused on measuring Nivolumab, Cabozantinib, Neoadjuvant, Immunotherapy, Liver Cancer, Borderline Resectable, Advance Resectable, Neoplasms, Hepatocellular Carcinoma, HCC, Resection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

Outcomes

Primary Outcome Measures

Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.
Number of patients who complete pre-op treatment and proceed to surgery.

Secondary Outcome Measures

Percentage of participants who obtain R0 resection.
Percentage of participants who obtain a pathologic complete response (CR).
Percentage of participants who obtain a major pathologic responses (MPR)
Objective response rate (ORR)
Median Overall Survival (OS)
Disease free survival (DFS)

Full Information

First Posted
September 27, 2017
Last Updated
March 24, 2023
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Exelixis, Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT03299946
Brief Title
Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)
Official Title
Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
May 14, 2018 (Actual)
Primary Completion Date
December 9, 2019 (Actual)
Study Completion Date
October 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Exelixis, Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Hepatocellular Carcinoma
Keywords
Nivolumab, Cabozantinib, Neoadjuvant, Immunotherapy, Liver Cancer, Borderline Resectable, Advance Resectable, Neoplasms, Hepatocellular Carcinoma, HCC, Resection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cabozantinib
Other Intervention Name(s)
XL184
Intervention Description
Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
OPDIVO, BMS 936558, MDX-1106, ONO-4538
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.
Time Frame
4 years
Title
Number of patients who complete pre-op treatment and proceed to surgery.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Percentage of participants who obtain R0 resection.
Time Frame
4 years
Title
Percentage of participants who obtain a pathologic complete response (CR).
Time Frame
4 years
Title
Percentage of participants who obtain a major pathologic responses (MPR)
Time Frame
4 years
Title
Objective response rate (ORR)
Time Frame
4 years
Title
Median Overall Survival (OS)
Time Frame
5 years
Title
Disease free survival (DFS)
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Laheru, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34796337
Citation
Ho WJ, Zhu Q, Durham J, Popovic A, Xavier S, Leatherman J, Mohan A, Mo G, Zhang S, Gross N, Charmsaz S, Lin D, Quong D, Wilt B, Kamel IR, Weiss M, Philosophe B, Burkhart R, Burns WR, Shubert C, Ejaz A, He J, Deshpande A, Danilova L, Stein-O'Brien G, Sugar EA, Laheru DA, Anders RA, Fertig EJ, Jaffee EM, Yarchoan M. Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumor Immunity. Nat Cancer. 2021 Sep;2(9):891-903. doi: 10.1038/s43018-021-00234-4. Epub 2021 Jul 29.
Results Reference
derived

Learn more about this trial

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

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