Neoadjuvant Anti-PD1 in HCC

Neoadjuvant Immunotherapy With Anti-PD1 in Borderline Resectable Hepatocellular Carcinoma

This is a phase 2, single-arm trial designed to assess the clinical benefit of treatment with nivolumab administered in patients with untreated, borderline resectable HCC.

Study Overview

• Status: Completed
• Conditions: HCC; Hepatocellular Carcinoma; Liver Cancer
• Intervention / Treatment: Drug: Nivolumab; Procedure: Hepatectomy

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed written informed consent form prior to the screening procedures.
2. Age ≥ 18 years.
3. Histological proof of HCC.
4. Willingness to undergo a pre-dosing fresh tumour biopsy. Patients for whom fresh biopsy may not be feasible will be ineligible for enrollment.
5. Intermediate or locally-advanced HCC (according to HKLC tumour status categorization) with the option of resection for potential cure as assessed by surgeon.
6. Child-Pugh score ≤ 7 with no symptomatic ascites or ascites requiring therapeutic paracentesis.
7. ECOG performance status ≤ 1.
8. Life expectancy of ≥ 12 weeks.
9. Adequate organ function (blood transfusion or use of biologic response modifiers is not permitted).
10. Measurable disease according to RECIST v1.1.
11. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception.
12. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception.
13. Able and willing to meet all protocol-required treatments, investigations and visits.

Exclusion Criteria:

1. Patients who have history of organ transplantation.
2. History of allergy or hypersensitivity to study drug components.
3. Patients who have active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition adequately treated with hormonal replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger or deemed by the investigator not to affect safety assessment.
4. Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
5. Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).
6. Receipt of any cancer therapy in the pre-operative period.
7. Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicine) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
8. Active, acute, or chronic clinically significant infections requiring therapy with the exception of hepatitis B or C virus infection. Patients with chronic HBV infection must be on antiviral therapy and have HBV DNA < 500 IU/ml. Active or chronic co-infection with hepatitis B and C, or hepatitis B and D is not allowed.
9. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
10. Symptomatic congestive heart failure, defined as ≥ Class II of the New York Heart Association functional classification system or known LVEF < 50% at baseline.
11. Active angina pectoris or recent myocardial infarction (within 6 months).
12. Chronic atrial fibrillation or QTcF > 470 msec.
13. History of other previous cancer that would interfere with the determination of safety or efficacy of nivolumab with respect to HCC.
14. Women who are pregnant or breast-feeding.
15. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment	Drug: Nivolumab; 3 mg/kg on Day 1 of each 2-weekly cycle for 3 doses; Procedure: Hepatectomy; Hepatectomy will be performed approximately 2 weeks after the 3rd dose of nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological tumour response rate	Proportion of patients with resected tumours having ≥30% necrosis	After surgery (normally 6 weeks after the start of nivolumab)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	The time from resection to disease recurrence or death from any cause	At least 3 months after surgery
Overall survival	The time from start of treatment to the date of death from any cause or last follow-up date	At least 3 months after surgery
Short-term surgery outcomes	Operation time, blood loss during surgery, transfusion requirement during surgery, and complication rate within 2 weeks following surgery	2 weeks after surgery
Safety and tolerability of nivolumab	The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analyses	Exploration of potential biomarkers predicting treatment response to nivolumab using biological specimens collected	within 1 year after treatment completion of the last subject

Collaborators and Investigators

• Sponsor: Dr Tan-to CHEUNG
• Investigators: Principal Investigator: Tan-to Cheung, MD, The University of Hong Kong

Publications and helpful links

Helpful Links

• HKU Clinical Trials Registry record

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 3, 2020
• Primary Completion (ACTUAL): December 31, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (ACTUAL): July 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2023
• Last Update Submitted That Met QC Criteria: January 31, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-7KU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No