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

NCT03299946 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: J17136IRB00149350
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

Nivolumab; Cabozantinib; Neoadjuvant; Immunotherapy; Liver Cancer; Borderline Resectable; Advance Resectable; Neoplasms; Hepatocellular Carcinoma; HCC; Resection

Outcome Measures

Primary Outcomes (2)

• Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.

  4 years

• Number of patients who complete pre-op treatment and proceed to surgery.

  4 years

Secondary Outcomes (6)

• Percentage of participants who obtain R0 resection.

  4 years

• Percentage of participants who obtain a pathologic complete response (CR).

  4 years

• Percentage of participants who obtain a major pathologic responses (MPR)

  4 years

• Objective response rate (ORR)

  4 years

• Median Overall Survival (OS)

  5 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: Cabozantinib; Drug: Nivolumab

Interventions

Cabozantinib DRUG

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

Also known as: XL184

Arm 1

Nivolumab 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.

Also known as: OPDIVO, BMS 936558, MDX-1106, ONO-4538

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Exelixis: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Related Publications (2)

• 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.

  PMID: 37723590 DERIVED

• 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.

  PMID: 34796337 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Neoplasms; Carcinoma, Hepatocellular

Interventions

cabozantinib; Nivolumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daniel Laheru, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 3, 2017
• Study Start: May 14, 2018
• Primary Completion: December 9, 2019
• Study Completion: October 1, 2021
• Last Updated: September 3, 2024

Record last verified: 2024-08

Locations

US (1)