Immunotherapy With Nivolumab in Combination With Lenvatinib for Advanced Stage Hepatocellular Carcinoma

NCT03841201 | Completed Phase 2 DMC

• 1 other identifier: IMMUNIB
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is an exploratory, open-label, single arm, multicenter phase II trial for the evaluation of efficacy and feasibility (as determined by safety and tolerability) of immunotherapy with nivolumab in combination with lenvatinib for patients with multinodular, advanced stage hepatocellular carcinoma in first line therapy

Conditions

Advanced Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR) according to RECIST 1.1

  Number and percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST 1.1

  6 months

• Safety and tolerability (AEs, SAEs according to NCI-CTCAE V 4.03)

  Type, incidence and severity of AEs, SAEs according to NCI-CTCAE V 4.03

  6 months

Secondary Outcomes (5)

• Objective response rate (ORR) according to iRECIST

  6 months

• Time-to-progression (TTP)

  6 months

• Progression free survival (PFS)

  6 months

• Overall survival (OS)

  6 months

• Translational research

  6 months

Study Arms (1)

Treatment

EXPERIMENTAL

* Lenvatinib peroral qd (8 mg for patients with body weight \<60kg and 12 mg for patients with body weight ≥ 60kg) * Nivolumab i.v. q2w (240mg fixed dose IV) max. 36 cycles

Drug: Lenvatinib; Drug: Nivolumab

Interventions

Lenvatinib DRUG

oral

Also known as: Study treatment

Treatment

Nivolumab DRUG

iv infusion

Also known as: Study treatment

Treatment

Eligibility Criteria

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

You may qualify if:

• Fully-informed written consent.
• Males and females ≥ 18 years of age
• \*There are no data that indicate special gender distribution. Therefore patients will be enrolled in the study gender-independently.
• Unresectable, multinodular tumour, not eligible for resection or local ablation
• Histologically confirmed diagnosis of hepatocellular carcinoma
• Has a Child-Pugh Classification score ≤ 6 for assessed liver function within 7 days before allocation (Appendix 4: Child-Pugh Score)
• At least one measurable site of disease as defined by RECIST 1.1 criteria with spiral CT scan or MRI.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, hepatic and renal function including the following:
• Haemoglobin ≥ 10.0 g/dL, absolute neutrophil count ≥ 1,500 /µL, platelets ≥70,000 /µL;
• Total bilirubin ≤ 3.0 mg/dL upper normal limit;
• AST (SGOT), ALT (SGPT) ≤ 5 x upper normal limit;
• International normalized ratio (INR) ≤1.25;
• Albumin ≥ 30 g/dL;

You may not qualify if:

• Previous systemic therapy in the first-line setting.
• Patients on a liver transplantation list or with advanced liver disease as defined below:
• Encephalopathy
• Untreatable Ascites.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Prior organ allograft or allogeneic bone marrow transplantation.
• Local therapies ongoing or completed \<4 weeks prior to the baseline scan.
• Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
• Prior, systemic anti-cancer chemotherapy, radiotherapy administered \<4 weeks prior to study entry, endocrine- or immunotherapy or use of other investigational agents.
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Major surgery within 4 weeks of starting the study. Patients must have recovered from effects of major surgery.
• Uncontrolled hypertension.
• Clinically significant cardiovascular disease.
• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive study drug.
• Proteinuria (≥2g/24h)

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Bristol-Myers Squibb: collaborator
• Eisai GmbH: collaborator

Study Sites (1)

Hannover Medical School

Hanover, 30625, Germany

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; Pharmaceutical Preparations; Nivolumab

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

Study Officials

• Salah-Eddin Al-Batran, MD

  Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, single-arm, multicenter phase II trial

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 15, 2019
• Study Start: June 12, 2019
• Primary Completion: October 27, 2022
• Study Completion: May 2, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)