Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)
PRIMER-1
PRIMER-1 Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)
1 other identifier
interventional
60
1 country
11
Brief Summary
This is a multicentre randomised 3-arm phase II clinical trial in patients with resectable Hepatocellular Carcinoma (HCC). Sixty patients will be randomized 1:1:1 to 6 weeks of pre-operative therapy with: pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib followed by up to 12 months treatment with post-operative pembrolizumab. The aim of the study is to compare the efficacy of pembrolizumab combined with lenvatinib with that of pembrolizumab and lenvatinib alone in terms of major pathological response in patients with resectable HCC. Major pathological response will be defined by the proportion of patients with less than 10% viable tumour at resection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 hepatocellular-carcinoma
Started Aug 2022
Longer than P75 for phase_2 hepatocellular-carcinoma
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2021
CompletedFirst Posted
Study publicly available on registry
January 11, 2022
CompletedStudy Start
First participant enrolled
August 25, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2030
December 6, 2024
December 1, 2024
5.9 years
November 2, 2021
December 3, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Major pathological response rate, defined as the proportion of patients with less than 10% viable tumour at resection.
The primary aim of the study is to test the hypothesis that the combination of pembrolizumab and lenvatinib result in a higher rate of major pathological response than either drug used as a single-agent in patients with resectable hepatocellular carcinoma.
At 4 months
Secondary Outcomes (8)
Percentage of viable tumour cells at resection
At 4 months
Radiological response rate
Evaluated pre-surgery (at 2 months)
Relapse free survival at 12 months from surgery
12 months from surgery
Proportion of patients with surgery delayed by more than 4 weeks from the planned surgery date
Evaluated by time to surgery (at 3 months)
30-day post-operative surgical complication rate
Evaluated 30 days post surgery
- +3 more secondary outcomes
Study Arms (3)
Pembrolizumab
ACTIVE COMPARATORLenvatinib.
ACTIVE COMPARATORPembrolizumab and Lenvatinib.
EXPERIMENTALInterventions
Pre-operative Lenvatinib (8 or 12mg PO once daily according to bodyweight \<60gk≥) for 6 weeks
Pre-operative combination of pembrolizumab and lenvatinib at the standard doses and duration as per cohort 1 and 2
Eligibility Criteria
You may qualify if:
- Have a diagnosis of Hepatocellular Carcinoma (HCC) confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) and suitable for surgical resection. Radiological confirmation of diagnosis is provided by the study site and defined by the presence of a liver mass of at least 1 cm and exhibiting arterial hypervascularity with washout in the portal venous phase seen in a tri-phasic magnetic resonance imaging (MRI).
- Measurable disease based on RECIST 1.1
- HCC amenable to R0 resection with curable intent
- Child-Pugh A liver disease
- International normalised ratio (INR) ≤1.4
- ECOG Performance status 0 or 1
- Adequate haematological function as defined by:
- Haemoglobin (Hb) \> 90g/l
- Neutrophil Count \> 1.5 x 109/l
- Platelets \> 75 x 109/l
- Adequate renal function with GFR \>40ml/min using a validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula)
- Adequate liver function as defined by:
- Aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5.0 x ULN
- Albumin \>32g/l
- Amylase ≤ 1.5 x ULN
- +9 more criteria
You may not qualify if:
- Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for advanced/unresectable HCC.
- Has received local therapy including trans arterial embolic, chemo- or radiotherapy, external beam radiotherapy or ablative therapy to the measurable lesion to be resected.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, or CD137).
- Oesophageal or gastric variceal bleeding within the last 6 months.
- Has received a live vaccine within 30 days prior to registration (seasonal flu vaccines that do not contain live virus are permitted). Administration of killed vaccines is allowed.
- Active autoimmune disease that has required systemic treatment (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs) in past 2 years except
- Vitiligo
- Psoriasis
- Autoimmune-related hyperthyroidism
- Autoimmune-related hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone replacement therapy (e.g., levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- A diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10mg daily prednisolone equivalent) or any other form of immunosuppressive therapy within 7 days prior to treatment.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has clinical or radiological evidence of ascites on physical examination that is not controlled with medication.
- Uncontrolled blood pressure (Systolic BP)\>150 mmHg or diastolic BP \>90 mmHg) with no change in anti-hypertensive medications within 1 week prior to randomisation.
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (11)
Queen Elizabeth Hospital
Birmingham, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
St James's Hospital
Leeds, United Kingdom
Clatterbridge Cancer Centre
Liverpool, United Kingdom
Hammersmith Hospital
London, United Kingdom
King's College Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
Freeman Hospital
Newcastle upon Tyne, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tim Meyer, BSc MBBS PhD FRCP
University College, London
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 2021
First Posted
January 11, 2022
Study Start
August 25, 2022
Primary Completion (Estimated)
July 1, 2028
Study Completion (Estimated)
July 1, 2030
Last Updated
December 6, 2024
Record last verified: 2024-12