Safety and Bioactivity of Ipilimumab and Nivolumab Combination Prior to Liver Resection in Hepatocellular Carcinoma

NCT03682276 | Unknown Phase 1 DMC FDA Drug

• 3 other identifiers: C/36/20172018-000987-27CA209-9LC
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. Participants will receive two doses of nivolumab and a single dose of ipilimumab in the weeks before their planned surgery.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Delay to surgery

  Number of patients with an unplanned delay to surgery to Day 89 or later

  Up to Day 89

• Incidence of treatment-emergent 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

  Up to Day 127

Secondary Outcomes (2)

• Objective response rate

  Up to Day 43

• Pathologic response rate

  Up to Day 88 or up to liver resection, whichever came first

Study Arms (1)

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

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Ipilimumab is a monoclonal antibody given as an immunotherapy

Also known as: YERVOY

Treatment Group

Nivolumab BIOLOGICAL

Nivolumab is a monoclonal antibody given as an immunotherapy

Also known as: OPDIVO

Treatment Group

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Imperial College London: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, Greater London, W12 0HS, United Kingdom

RECRUITING

Related Publications (1)

• Pinato 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.

  PMID: 33757459 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• David J Pinato

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David J Pinato

CONTACT

02033131151; d.pinato@imperial.ac.uk

Frances Abomeli

CONTACT

02033138070; f.abomeli@imperial.ac.uk

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 20, 2018
• First Posted: September 24, 2018
• Study Start: March 1, 2019
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 13, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)