Clinical trial NCT03299946: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Hepatocellular Carcinoma
Keywords: Nivolumab
Cabozantinib
Neoadjuvant
Immunotherapy
Liver Cancer
Borderline Resectable
Advance Resectable
Neoplasms
Hepatocellular Carcinoma
HCC
Resection
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Exelixis
name: Bristol-Myers Squibb
First posted: 2017-10-03
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.
timeFrame: 4 years
measure: Number of patients who complete pre-op treatment and proceed to surgery.
timeFrame: 4 years
Secondary outcomes:
measure: Percentage of participants who obtain R0 resection.
timeFrame: 4 years
measure: Percentage of participants who obtain a pathologic complete response (CR).
timeFrame: 4 years
measure: Percentage of participants who obtain a major pathologic responses (MPR)
timeFrame: 4 years
measure: Objective response rate (ORR)
timeFrame: 4 years
measure: Median Overall Survival (OS)
timeFrame: 5 years
measure: Disease free survival (DFS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Daniel Laheru, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.