Hepatocellular CarcinomaPhase 1/2PRIME-HCCNCT03682276
Safety and Bioactivity of Ipilimumab and Nivolumab Combination Prior to Liver Resection in Hepatocellular Carcinoma
A Phase 1/2 study testing Ipilimumab and Nivolumab in people with Hepatocellular Carcinoma, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The PRIME-HCC trial will assess the effects of combination treatment with nivolumab (OPDIVO) and ipilimumab (YERVOY) pre-operatively in hepatocellular carcinoma patients for whom liver resection is planned. The trial will be conducted at a small number of National Health Service hospitals in the UK. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Ipilimumab and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2019to 12 Mar 2026
- Phase
- Phase 1/2
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
- Written informed consent for the trial.
- Aged ≥18 years
- Confirmed diagnosis of HCC
- Willing to provide tissue from an excisional biopsy of a tumour lesion
- Have measurable disease by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI) defined by RECIST 1.1 criteria
- Ineligible for liver transplantation
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- Medically fit to undergo surgery as determined by the treating medical and surgical oncology team
- ECOG performance status 0 or 1
- Adequate organ function
- Overall Child-Pugh class A
- Female patient of childbearing potential should have a negative serum pregnancy test within 24 h of her first dose of IMP
- Women of childbearing potential must be willing to use a highly effective method of contraception for the course of the study through 5 months after the last dose of Investigational Medicinal Product (IMP). Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
- Sexually active males must agree to use an adequate method of contraception starting with the first dose of IMP through 7 months after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
Who cannot join
- Extrahepatic metastasis
- Prior systemic anticancer treatment for HCC, including an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
- Prior orthotopic liver transplantation
- Any major surgery within the 3 weeks prior to enrolment
- Hepatic encephalopathy
- Ascites that is refractory to diuretic therapy
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- Is currently receiving anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy or biologic therapy) or has participated or is participating in a study of an IMP or used an investigational device within 4 weeks of the first dose of IMP
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy
- Known history of active Bacillus Tuberculosis (TB)
- History of known hypersensitivity to any monoclonal antibody or any of their excipients
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Known history of, or any evidence of active, non-infectious pneumonitis
- Active infection requiring systemic therapy, with exceptions relating to Hepatitis B and C virus infection
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Principal Investigator (PI)
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Pregnant or breastfeeding
- Known history of Human Immunodeficiency Virus (HIV; HIV 1/2 antibodies)
- Received a live vaccine within 30 days of first dose of IMP administration. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, Greater London, W12 0HS
About this study
Official title: PRIME-HCC: Preliminary Assessment of Safety and Bioactivity of the Ipilimumab and Nivolumab Combination Prior to Liver Resection (LR) in Hepatocellular Carcinoma (HCC)
The PRIME-HCC trial will assess the effects of combination treatment with nivolumab (OPDIVO) and ipilimumab (YERVOY) pre-operatively in hepatocellular carcinoma patients for whom liver resection is planned. The trial will be conducted at a small number of National Health Service hospitals in the UK. Participants will receive two doses of nivolumab and a single dose of ipilimumab in the weeks before their planned surgery.
Read the detailed description
This is a single-arm, open-label study to be conducted in 32 patients at a small number of UK hospitals. The study is in 2 parts: Part 1 will confirm, in a small number of patients, that the treatment regimen is safe and doesn't result in unacceptable delay to liver resection. Part 2 will expand the number of patients studied, and provide the opportunity to assess survival over about 2 years after liver resection. The decision to proceed to Part 2 will be taken with advice from an independent, expert committee.
Patients with early-stage HCC will first undergo screening procedures during a 28-day time window between giving consent and starting drug treatment. Screening procedures will include:
- Medical interview and physical exam
- ECG
- Tumour biopsy
- Tumour imaging by MRI
- Tumour imaging by CT
- Blood and urine samples
- Stool sample (optional)
Patients meeting the protocol-specified criteria will be enrolled and on Day 1 will have the following:
- Medical interview, and physical exam (if required)
- Blood and urine samples
- Intravenous dose of ipilimumab ('YERVOY') 1 milligram per kilogram body weight
- Intravenous dose of nivolumab ('OPDIVO') 3 milligrams per kilogram body weight
On Day 22 the participants will have the following:
- Medical interview, and physical exam (if required)
- Blood and urine samples
- Intravenous dose of nivolumab ('OPDIVO') 3 milligrams per kilogram body weight
On Day 43 the participants will have the following:
- Medical interview, and physical exam (if required)
- ECG
- Tumour imaging by MRI
- Blood and urine samples
- Stool sample (optional)
Patients who remain eligible for liver resection will likely undergo surgery within a few days of the Day 43 visit.
On Day 127 the participants will have the following:
- Medical interview, and physical exam (if required)
- Tumour imaging by MRI
- Blood and urine samples
Every 4 months thereafter until 2 years later, or until starting another anti-cancer treatment, participants will have tumour imaging by MRI.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Ipilimumab, Nivolumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabBiological
Also called YERVOY
Ipilimumab is a monoclonal antibody given as an immunotherapy
NivolumabBiological
Also called OPDIVO
Nivolumab is a monoclonal antibody given as an immunotherapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | Ipilimumab, solution for infusion, 1 milligram per kilogram body weight, once every 3 weeks, for 3 weeks; Nivolumab, solution for infusion, 3 milligrams per kilogram body weight, once every 3 weeks, for 6 weeks Receives: Biological: Ipilimumab; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delay to Surgery
Number of patients with an unplanned delay to surgery to Day 89 or later
Measured: Up to Day 89
Frequency of Treatment-related Adverse Events [Safety and Tolerability]
Safety and tolerability of the nivolumab and ipilimumab combination based on NCI CTCAE v5.0 criteria from the day of first nivolumab and ipilimumab administration to 126 days later. Treatment-related adverse events (TRAE) are defined as any unfavorable medical occurrence, symptom, or abnormal laboratory finding in a participant that is deemed to be either definitely, probably, or possibly caused by the trial treatment.
Measured: Up to Day 127
Secondary outcomes (2)
Objective Response Rate
Objective response rate (complete or partial response) on pre-resection imaging 42 days after the day of first nivolumab and ipilimumab administration using Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. The criteria classifies response based on the assessment of target and non-target lesions on scans as:
Complete Response (CR): requires all of:
- disappearance of all target and non-target lesions
- pathological lymph nodes must have reduced to <10 mm in short axis
- no new lesions
Partial Response (PR): requires all of:
- at least 30% decrease in sum of diameters (SOD) of target lesions compared to baseline sum diameters
- non-progressive disease of non-target lesions
- no new lesions
Progressive Disease (PD): either one of:
- any new lesions
- at least 20% relative and 5 mm absolute increase of SOD of target lesions compared to smallest SOD ever recorded for the patient
Stable Disease (SD): not meeting criteria for PD or PR.
Measured: Up to Day 43
Pathologic Response Rate
Pathologic response rate (≥70%) on hematoxylin and eosin evaluation of the resected specimen.
Measured: Up to Day 88 or up to liver resection, whichever came first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start1 Mar 2019
- Primary completion12 Mar 2026
- Study completion12 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- David J Pinato, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03682276
- Sponsor's protocol ID
- C/36/2017
- Other IDs
- 2018-000987-27, CA209-9LC, 2018
- Acronym
- PRIME-HCC
- Status last verified
- Jun 2026
- First submitted
- 20 Sep 2018
- Last updated
- 29 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
D'Alessio A, Stefanini B, Blanter J, Adegbite B, Crowley F, Yip V, Slater S, Fulgenzi CAM, Celsa C, Manfredi GF, Pai M, Goldin RD, Ward SC, Fiel MI, Shu DH, Su YY, Cortellini A, Baretti M, Anders R, Yarchoan M, Hsu C, Marron TU, Pinato DJ. Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis. Lancet Oncol. 2024 Nov;25(11):1465-1475. doi: 10.1016/S1470-2045(24)00457-1. Epub 2024 Oct 19.
PubMed 39437804Pinato DJ, Cortellini A, Sukumaran A, Cole T, Pai M, Habib N, Spalding D, Sodergren MH, Martinez M, Dhillon T, Tait P, Thomas R, Ward C, Kocher H, Yip V, Slater S, Sharma R. PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma. BMC Cancer. 2021 Mar 23;21(1):301. doi: 10.1186/s12885-021-08033-x.
PubMed 33757459