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

Locally Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03299946
• Other study ID #: J17136
• Secondary ID: IRB00149350
• Status: Completed
• Phase: Phase 1
• Start date: May 14, 2018
• Est. completion date: October 1, 2021

Study information

• Verified date: March 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: October 1, 2021
• Est. primary completion date: December 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Locally Advanced Hepatocellular Carcinoma

Intervention

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

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Bristol-Myers Squibb, Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.		4 years
Primary	Number of patients who complete pre-op treatment and proceed to surgery.		4 years
Secondary	Percentage of participants who obtain R0 resection.		4 years
Secondary	Percentage of participants who obtain a pathologic complete response (CR).		4 years
Secondary	Percentage of participants who obtain a major pathologic responses (MPR)		4 years
Secondary	Objective response rate (ORR)		4 years
Secondary	Median Overall Survival (OS)		5 years
Secondary	Disease free survival (DFS)		5 years