Locally Advanced Hepatocellular CarcinomaPhase 1NCT03299946
Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)
A Phase 1 study testing Cabozantinib and Nivolumab in people with Locally Advanced Hepatocellular Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Hepatocellular Carcinoma
- What is being tested?
- Cabozantinib and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2018to 1 Oct 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Any certain study-specified heart conditions 6 months prior to enrollment.
- Major surgery within 2 months before enrollment.
- Have any evidence of moderate or severe ascites.
- Any untreated or incompletely treated varices with bleeding or high-risk bleeding.
- Inability to swallow intact tablets.
- Known or suspected hypersensitivity to study treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
About this study
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.
- Being tested
- Cabozantinib, Nivolumab
- Keywords
- Nivolumab, Cabozantinib, Neoadjuvant, Immunotherapy, Liver Cancer, Borderline Resectable, Advance Resectable, Neoplasms, Hepatocellular Carcinoma, HCC, Resection
- Medical subject headings
- Liver Neoplasms, Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL184
Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.
NivolumabDrug
Also called OPDIVO, BMS 936558, MDX-1106, ONO-4538
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: Cabozantinib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.
Measured: 4 years
Number of patients who complete pre-op treatment and proceed to surgery.
Measured: 4 years
Secondary outcomes (6)
Percentage of participants who obtain R0 resection.
Measured: 4 years
Percentage of participants who obtain a pathologic complete response (CR).
Measured: 4 years
Percentage of participants who obtain a major pathologic responses (MPR)
Measured: 4 years
Objective response rate (ORR)
Measured: 4 years
Median Overall Survival (OS)
Measured: 5 years
Disease free survival (DFS)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start14 May 2018
- Primary completion9 Dec 2019
- Study completion1 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Daniel Laheru, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03299946
- Sponsor's protocol ID
- J17136
- Other IDs
- IRB00149350
- Status last verified
- Aug 2024
- First submitted
- 27 Sep 2017
- Last updated
- 3 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 37723590Ho 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.
PubMed 34796337
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility and Efficacy of Neoadjuvant Cabozantinib Plus Nivolumab (CaboNivo) Followed by Definitive Resection for Patients With Locally Advanced Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT03299946
- Acronym / sponsor ID
- J17136
- Keywords
- Nivolumab, Cabozantinib, Neoadjuvant, Immunotherapy, Liver Cancer, Borderline Resectable, Advance Resectable, Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Exelixis, Bristol-Myers Squibb
- Study start
- 14 May 2018 (actual)
- Primary completion
- 9 Dec 2019 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 3 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Cabozantinib, Drug: Nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabozantinibAlso: XL184Cabozantinib (40mg) will be taken by mouth daily for 8 weeks. | Drug | Arm 1 |
| NivolumabAlso: OPDIVO, BMS 936558, MDX-1106, ONO-4538Nivolumab 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. | Drug | Arm 1 |
Primary outcome
Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab.
Time frame: 4 years
Number of patients who complete pre-op treatment and proceed to surgery.
Time frame: 4 years
6 secondary outcomes
Percentage of participants who obtain R0 resection.
Time frame: 4 years
Percentage of participants who obtain a pathologic complete response (CR).
Time frame: 4 years
Percentage of participants who obtain a major pathologic responses (MPR)
Time frame: 4 years
Objective response rate (ORR)
Time frame: 4 years
Median Overall Survival (OS)
Time frame: 5 years
Disease free survival (DFS)
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Derived from this study: PubMed 37723590Zhang 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.
- Derived from this study: PubMed 34796337Ho 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Laheru, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cabozantinib and Nivolumab in people with Locally Advanced Hepatocellular Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab. (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03299946, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2024.