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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)

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ClinicalTrials.gov Identifier: NCT03299946
Recruitment Status : Recruiting
First Posted : October 3, 2017
Last Update Posted : November 7, 2018
Sponsor:
Collaborators:
Exelixis
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Locally Advanced Hepatocellular Carcinoma Drug: Cabozantinib Drug: Nivolumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)
Actual Study Start Date : January 24, 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1 Drug: Cabozantinib
Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.
Other Name: XL184

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.
Other Name: OPDIVO, BMS 936558, MDX-1106, ONO-4538




Primary Outcome Measures :
  1. Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab. [ Time Frame: 4 years ]
  2. Number of patients who complete pre-op treatment and proceed to surgery. [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Percentage of participants who obtain R0 resection. [ Time Frame: 4 years ]
  2. Percentage of participants who obtain a pathologic complete response (CR). [ Time Frame: 4 years ]
  3. Percentage of participants who obtain a major pathologic responses (MPR) [ Time Frame: 4 years ]
  4. Objective response rate (ORR) [ Time Frame: 4 years ]
  5. Median Overall Survival (OS) [ Time Frame: 5 years ]
  6. Disease free survival (DFS) [ Time Frame: 5 years ]


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03299946


Contacts
Contact: Jane Zorzi 410-614-5818 jzorizi1@jhmi.edu
Contact: Mark Yarchoan, MD 410-955-8893 mark.yarchoan@jhmi.edu

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Susan Sartorius-Mergenthaler, MA, RN    410-614-3644    Sartosu@jhmi.edu   
Contact: Jane Zorzi, BSN, RN    410-614-5818    jzorzi1@jhmi.edu   
Sub-Investigator: Daniel Laheru, MD         
Principal Investigator: Mark Yarchoan, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Exelixis
Bristol-Myers Squibb
Investigators
Principal Investigator: Daniel Laheru, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03299946     History of Changes
Other Study ID Numbers: J17136
IRB00149350 ( Other Identifier: Johns Hopkins University )
First Posted: October 3, 2017    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Nivolumab
Cabozantinib
Neoadjuvant
Immunotherapy
Liver Cancer
Borderline Resectable
Advance Resectable
Neoplasms
Hepatocellular Carcinoma
HCC
Resection

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs