NIVOLUMAB for Hepatocellular carcinoma | Intermediate-stage hepatocellular carcinoma

Inclusion criteria

• {"criterion_text":"- Histological diagnosis of HCC and at least one uni-dimensional lesion measurable according to RECIST 1.1 criteria by CT-scan or MRI.\n- HAP score A, B or C\n- No contra-indications to T-cell checkpoint inhibitor therapy (use of immunosuppressive drugs including steroids at dose equivalent to prednisolone >10mg/day unless used as replacement therapy; organ transplantation; subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, lichen planus or other conditions not expected to recur in the absence of an external trigger are permitted to enrol) (not applicable for France)\n- Women of child-bearing potential should have a negative pregnancy test prior to study entry. Both men and women must be using an adequate contraception method, which must be continued for 5 months after completion of treatment for women and 7 months for men\n- Written informed consent (not applicable for France)\n- Aged ≥ 18 years and estimated life expectancy ≥3 months (only for France)\n- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give her written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent. (only for France)\n- Patients must be affiliated to a Social Security System (or equivalent). (only for France)\n- Intermediate stage HCC (BCLC B) not candidate for surgical resection, ablation therapy or liver transplatation (only for France)\n- Not a candidate for surgical resection or liver transplantation (not applicable for France)\n- Aged ≥16 years and estimated life expectancy ≥3 months (not applicable for France)\n- ECOG performance status 0-1\n- Adequate haematological function: - Hb ≥9g/L - absolute neutrophil count ≥1.0x109 /L - platelet count ≥60x109 /L\n- Bilirubin ≤50 μmol/L; AST, ALT, and ALP ≤5 x ULN\n- Adequate renal function; Creatinine μmol/L ≤1.5 x ULN\n- INR ≤1.6\n- Child-Pugh A (score ≤6)"}

Exclusion criteria

• {"criterion_text":"- Extrahepatic metastasis\n- Documented occlusion of the hepatic artery or main portal vein\n- Hypersensitivity to intravenous contrast agents\n- Active clinically serious infection > Grade 2 NCI-CTC\n- Pregnant or lactating women\n- Known history of HIV infection\n- HBV chronic infection with HBV DNA > 500 IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated.\n- History of second malignancy except those treated with curative intent more than three years previously without relapse and non-melanotic skin cancer or cervical carcinoma in situ\n- Evidence of severe or uncontrolled systemic diseases, or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial\n- Psychiatric or other disorder likely to impact on informed consent\n- Patient is unable and/or unwilling to comply with treatment and study instructions\n- Prior embolisation, systemic or radiation therapy for HCC\n- Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity\n- evidence of uncontrolled, active infection, requiring parenteral antibacterial, anti-viral or antifungal therapy within 7 days prior to administration of study medication\n- Positive test for latent TB or evidence of active TB\n- Hypersensitivity to any of the active substances or excipients\n- Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment\n- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of study drug administration (not applicable for France)\n- Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative colitis\n- Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone 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 are permitted to enrol (not applicable for France)\n- Contra-indications to T-cell checkpoint inhibitor therapy: - Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of the first dose of study drug administration; unless used as replacement therapy - Organ transplantation - Active, known or suspected autoimmune disease Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, lichen planus or other conditions not expected to recur in the absence of an external trigger are permitted to enrol.\n- Any contraindications for hepatic embolisation procedures including portosystemic shunt, hepatofugal blood flow, known severe atheromatosis\n- Investigational therapy or major surgery within 4 weeks of trial entry\n- History of bleeding within the past 4 weeks\n- Child-Pugh cirrhosis B or C (score ≥7)\n- HAP score D\n- Hepatic encephalopathy\n- Ascites refractory to diuretic therapy"}

Primary endpoints

• {"endpoint_text":"- Phase II component : Time to TACE/TAE Progression (TTTP)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase III component : Overall Survival","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Phase II component : Number of Grade 3+ AEs and SAEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II component : Progression Free Survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II component : Time to progression (TTP)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II component : Response rate by RECIST 1.1","definition_or_measurement_approach":"Radiological response assessed according to RECIST 1.1"}
• {"endpoint_text":"- Phase III component : Time to TACE/TAE Progression (TTTP)","definition_or_measurement_approach":"Defined as the time between the date of randomisation and the date of progression confirmed by RECIST 1.1."}
• {"endpoint_text":"- Phase III component : Number of Grade 3+ AEs and SAEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase III component : Progression Free Survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase III component : Time to progression (TTP)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase III component : Objective response rate (ORR) by RECIST 1.1","definition_or_measurement_approach":"Objective response assessed by RECIST 1.1"}
• {"endpoint_text":"- Phase III component : EORTC QLQ_C30 EORTC QLQ-HCC18 EQ5D","definition_or_measurement_approach":"Health-related quality of life assessed using EORTC QLQ-C30, EORTC QLQ-HCC18 and EQ-5D questionnaires"}

France

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

17-04-2025

Processing Time Days

171

Number Of Sites

4

Number Of Participants

11

United Kingdom

Latest Decision Or Authorization Date

08-11-2024

Primary sponsor

Full Name

The Clatterbridge Cancer Centre NHS Foundation Trust

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

United Kingdom

Third parties

• {"country":"","full_name":"Bristol Myers Squibb Pharmaceuticals Ltd","duties_or_roles":"Source of monetary support / funder","organisation_type":""}