Phase II/III randomised study combining nivolumab with TACE treatment for patients with liver cancer.

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; Intermediate stage Hepatocellular Carcinoma; MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864

• Registration Number: EUCTR2018-000004-42-GB
• Lead Sponsor: The Clatterbridge Cancer Centre NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-18
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 522

Inclusion Criteria

1.Histological diagnosis* of HCC and at least one uni-dimensional lesion measurable according to RECIST 1.1 criteria by CT-scan or MRI.
2.Not a candidate for surgical resection or liver transplantation**
3.Aged =16 years and estimated life expectancy >3 months
4.ECOG performance status 0-1
5.Adequate haematological function:
•Hb =9g/L
•Absolute neutrophil count =1.0x109/L
•Platelet count =60x109/L
6.Bilirubin =50 µmol/L, AST,ALT and ALP =5 x ULN
7.Adequate renal function; Creatinine = 1.5ULN (Using Cockcroft-Gault Formula)
8.INR =1.6
9.Child-Pugh A (score =6) (Appendix D)
10.HAP score A, B or C (Appendix E)
11.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).
12.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
13.Written informed consent

*All patients are required to under a MANDATORY biopsy prior to entry onto the study.
**Criteria which establish ‘intermediate’ HCC
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 348

Exclusion Criteria

1.Extrahepatic metastasis
2.Prior embolisation, systemic or radiation therapy for HCC
3.Any contraindications for hepatic embolisation procedures including portosystemic shunt, hepatofugal blood flow, known severe atheromatosis
4.Investigational therapy or major surgery within 4 weeks of trial entry
5.History of bleeding within the past 4 weeks
6.Child-Pugh cirrhosis B or C (score =7)
7.HAP score D
8.Hepatic encephalopathy
9.Ascites refractory to diuretic therapy
10.Documented occlusion of the hepatic artery or main portal vein
11.Hypersensitivity to intravenous contrast agents
12.Active clinically serious infection > Grade 2 NCI-CTC
13.Pregnant or lactating women
14.Known history of HIV infection
15.HBV chronic infection with HBV DNA = 500 IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated.
16.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
17.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
18.Psychiatric or other disorder likely to impact on informed consent
19.Patient is unable and/or unwilling to comply with treatment and study instructions
20. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity
21. Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or antifungal therapy within 7 days prior to administration of study medication
22. Positive test for latent TB or evidence of active TB
23. Hypersensitivity to any of the active substances or excipients
24. Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment
25. 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
26. Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative colitis
27. 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified