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

NCT ID: NCT03299946

Last Updated: 2024-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-14
• Study Completion Date: 2021-10-01

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.

Conditions

Locally Advanced Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.

Nivolumab

Intervention Type: DRUG

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.

Interventions

Cabozantinib

Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

XL184; OPDIVO, BMS 936558, MDX-1106, ONO-4538

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Laheru, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

References

Zhang S, Yuan L, Danilova L, Mo G, Zhu Q, Deshpande A, Bell ATF, Elisseeff J, Popel AS, Anders RA, Jaffee EM, Yarchoan M, Fertig EJ, Kagohara LT. Spatial transcriptomics analysis of neoadjuvant cabozantinib and nivolumab in advanced hepatocellular carcinoma identifies independent mechanisms of resistance and recurrence. Genome Med. 2023 Sep 18;15(1):72. doi: 10.1186/s13073-023-01218-y.

Reference Type: DERIVED

PMID: 37723590 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34796337 (View on PubMed)

Other Identifiers

IRB00149350

Identifier Type: OTHER

Identifier Source: secondary_id

J17136

Identifier Type: -

Identifier Source: org_study_id