Hepatic Intra-Arterial Administration of Ipilimumab in Combination With Intra-venous Nivolumab for Advanced Hepatocellular Carcinoma

NCT04823403 | Recruiting Phase 1

• 2 other identifiers: 2020-003766-402020/3138
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To determine the Maximum Tolerated Dose (MTD), and the recommended Phase 2 dose of HIA Ipilimumab in combination with IV Nivolumab by monitoring the Dose Limiting Toxicity (DLT) within 1 month after IA Ipilimumab administration in dose-escalation phase.

  28 days

Study Arms (1)

Patients with hepatocellular carcinoma

EXPERIMENTAL

1. Intravenous Nivolumab (1mg/kg) will be given every 6 weeks for a maximal period of 6 months within the study. 2. Ipilimumab, single intra-arterial (IA) injection per patient, at 3 dose-levels\*. * (D1) Starting dose : 50 mg; n=3 to 6 * (D2) 2nd dose-level : 100 mg; n=3 to 6 * (D3) Maximal tested dose : 150mg; n=3 to 6 (if no limiting toxicities) \*Dose level (D-1) : 25 mg will be tested if de-escalation is needed at D1 (\>1/3 DLT at D1)

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Intravenous Nivolumab (1mg/kg) will be given every 6 weeks for a maximal period of 6 months within the study.

Patients with hepatocellular carcinoma

Ipilimumab DRUG

Ipilimumab, single intra-arterial (IA) injection per patient, at 3 dose-levels\*. * (D1) Starting dose : 50 mg; n=3 to 6 * (D2) 2nd dose-level : 100 mg; n=3 to 6 * (D3) Maximal tested dose : 150mg; n=3 to 6 (if no limiting toxicities) \*Dose level (D-1) : 25 mg will be tested if de-escalation is needed at D1 (\>1/3 DLT at D1)

Patients with hepatocellular carcinoma

Eligibility Criteria

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

You may qualify if:

• Adult Men and women ≥ 18 years old
• Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
• Patient should be able to comply with treatment, PK, and pharmacodynamic sample collection and willing to comply with study visits and procedures as per protocol.
• Patients must have pathological confirmation of HCC.
• Patient should be considered as non resectable by Multidisciplinary Team and liver surgeon, and non-eligible for liver transplantation (advanced HCC, BCLC C).
• Patient who progresses on, or is intolerant to, or has refused standard first line therapy and eligible for receiving IV infusion of Nivolumab and HIA administration of Ipilimumab
• Patient with active intrahepatic HCC. Part of the disease should not have undergone local treatments (including chemoembolization, or percutaneous targeted therapies).
• Patients with or without active viral infection (i.e., HCV, HBV) are eligible. Patients with active HBV/HCV are eligible provided they are adequately treated to control the disease.
• Patients should have measurable disease as defined by mRECIST criteria for response assessment.
• ECOG status of 0 or 1 (Appendix 2).
• Life expectancy of ≥ 12 weeks at the time of informed consent per Investigator assessment.
• Adequate organ function as defined by the following:
• White blood cells (WBCs) ≥ 2000/mL
• Neutrophils ≥ 1000/mL
• Platelets ≥ 75 × 103/mL

You may not qualify if:

• Patients with a prior malignancy are excluded, except those with prior malignancies treated more than 2 years previously (at the time of informed consent) with curative intent with no evidence of disease during the interval and who are considered by the Investigator to present a low risk for recurrence, will be eligible.
• A known or underlying medical condition that, in the opinion of the Investigator, could make the administration of study drug hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate study.
• Requirement for daily supplemental oxygen
• Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
• A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Any other significant acute or chronic medical illness. Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
• Subjects who are unable to undergo and/or tolerate venous AND arterial access (evaluated on pre-treatment imaging)
• Systemic or topical corticosteroids at immunosuppressive doses (≥ 10 mg/day of prednisone or equivalent)
• Any other investigational drug
• Any anticancer therapy (chemotherapy, biologics, therapeutic vaccines, radiotherapy, or hormonal treatment).
• Vaccines containing live virus
• Allergen hyposensitization therapy
• Growth factors, e.g., granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin
• Major surgery
• Bisphosphonates or anti-RANKL therapy

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, 94800, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver 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

Central Study Contacts

Lambros Tselikas, MD

CONTACT

+33 (0)1 42 11 42 11; lambros.tselikas@gustaveroussy.fr

Thibault RAOULT

CONTACT

+33 (0)1 42 11 42 11; thibault.raoult@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1, Dose-Escalation (3+3 design), Open-label, single arm, single-center study, and expansion cohort. DLT will be captured within 1 month after HIA administration. 3 levels of dose of HIA ipilimumab will be tested. Starting by a dose 5 times lower than what is used for IV administration.

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: March 30, 2021
• Study Start: November 13, 2020
• Primary Completion: November 4, 2022
• Study Completion: November 1, 2024
• Last Updated: July 26, 2024

Record last verified: 2024-07

Locations

FR (1)