Neoadjuvant Anti-PD1 in HCC

NCT05471674 | Completed Phase 2

• 1 other identifier: CA209-7KU
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma; HCC; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological tumour response rate

  Proportion of patients with resected tumours having ≥30% necrosis

  After surgery (normally 6 weeks after the start of nivolumab)

Secondary Outcomes (4)

• Recurrence-free survival

  At least 3 months after surgery

• Overall survival

  At least 3 months after surgery

• Short-term surgery outcomes

  2 weeks after surgery

• Safety and tolerability of nivolumab

  6 months

Other Outcomes (1)

• Exploratory analyses

  within 1 year after treatment completion of the last subject

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Nivolumab; Procedure: Hepatectomy

Interventions

Nivolumab DRUG

3 mg/kg on Day 1 of each 2-weekly cycle for 3 doses

Treatment

Hepatectomy PROCEDURE

Hepatectomy will be performed approximately 2 weeks after the 3rd dose of nivolumab

Treatment

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Patients who have history of organ transplantation.
• History of allergy or hypersensitivity to study drug components.
• 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.
• 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.
• 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).
• Receipt of any cancer therapy in the pre-operative period.
• 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.
• 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.
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Symptomatic congestive heart failure, defined as ≥ Class II of the New York Heart Association functional classification system or known LVEF \< 50% at baseline.
• Active angina pectoris or recent myocardial infarction (within 6 months).
• Chronic atrial fibrillation or QTcF \> 470 msec.
• History of other previous cancer that would interfere with the determination of safety or efficacy of nivolumab with respect to HCC.
• Women who are pregnant or breast-feeding.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results.

Sponsors & Collaborators

• Dr Tan-to CHEUNG: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Related Links

• HKU Clinical Trials Registry record

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Nivolumab; Hepatectomy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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; Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Tan-to Cheung, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: July 4, 2022
• First Posted: July 25, 2022
• Study Start: July 3, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: February 1, 2023

Record last verified: 2023-01

Locations

HK (1)