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Advanced Hepatocellular CarcinomaPhase 2NCT03841201

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

A Phase 2 study testing Lenvatinib and Nivolumab in people with Advanced Hepatocellular Carcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Hepatocellular Carcinoma
What is being tested?
Lenvatinib and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteGermany
Study dates
12 Jun 2019to 2 May 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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;
  • Creatinine ≤ 1.5 x upper normal limit OR measured or calculated creatinine clearance (according to Cockcroft-Gault) ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (GFR can also be used in place of creatinine or CrCl)
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. Women must not be breastfeeding.
  • If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria:
  • Patients with HBV or HCV infection should be monitored for viral levels during study participation.
  • Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA < 100 IU/ml and should be managed per local treatment guidelines.
  • Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the time point of enrollment into the study by the latest and treatment is continued during study participation and for ≥ 6 months after end of study treatment.
  • HCV patients with with advanced HCC are mostly not treated for their HCV infection. However, patients treated for HCV are considered suitable for inclusion if antiviral therapy has been completed ≥ 30 days prior to first administration of study drug.
  • The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
  • WOCBP must agree to follow instructions for method(s) of contraception for a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo 5 half-lives. The terminal half-lives of nivolumab is approximately 25 days. WOCBP should use an adequate method to avoid pregnancy for approximately 5 months (30 days plus the time required for nivolumab to undergo 5 half-lives) after the last dose of investigational drug.
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo 5 half-lives. The terminal half-lives of nivolumab is approximately 25 days. Males who are sexually active with WOCBP must continue contraception for approximately 7 months (90 days plus the time required for nivolumab to undergo 5 half-lives) after the last dose of investigational drug. In addition, male subjects must be willing to refrain from sperm donation during this time.

Who cannot join

  • 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.
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  • 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.
  • Malignancies other than disease under study within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
  • 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)
  • Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol.
  • Subjects with a history of or current CNS metastases. A scan to confirm the absence of brain metastases is not required. Patients with unknown CNS metastatic status and any clinical signs indicative of CNS metastases are eligible if CNS metastases are excluded using CT and/or MRI scans.
  • Pregnant or breast-feeding women.
  • Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the medical monitor be consulted prior to signing informed consent.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • All toxicities attributed to prior anti-cancer therapy other than hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug.
  • > Grade 1 peripheral neuropathy according to CTCAE version 4.03
  • Patients who have received a live vaccine within 30 days prior to enrolment.
  • History of allergy or hypersensitivity to study drugs or any constituent of the products
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Hannover Medical School

    Hanover, 30625

Other trials in Germany

About this study

Official title: IMMUNIB - An Open-label, Single-arm Phase II Study of Immunotherapy With Nivolumab in Combination With Lenvatinib for Advanced Stage Hepatocellular

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

Being tested
Lenvatinib, Nivolumab
Keywords
hepatocellular carcinoma
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Also called Study treatment

    oral

  • NivolumabDrug

    Also called Study treatment

    iv infusion

Study groups in NCT03841201
Study groupRoleWhat they receive
TreatmentExperimental* 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
Receives: Drug: Lenvatinib; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 6 months

  2. 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

    Measured: 6 months

Secondary outcomes (5)

  1. Objective response rate (ORR) according to iRECIST

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

    Measured: 6 months

  2. Time-to-progression (TTP)

    Time from the date of treatment allocation to the date of first observed disease progression (investigator assessment according to RECIST 1.1).

    Measured: 6 months

  3. Progression free survival (PFS)

    Time from the date of treatment allocation to the date of first observed disease progression (investigator assessment according to RECIST 1.1) or death from any cause.

    Measured: 6 months

  4. Overall survival (OS)

    Time from the date of treatment allocation to the date of death (due to any cause).

    Measured: 6 months

  5. Translational research

    Correlation of biomarkers potentially associated with clinical efficacy (OS, PFS and ORR) from lenvatinib plus nivolumab by molecular quantitation of mRNA expression of parameters like e.g. PD-1, PD-L1 and PD-L2, immune cell infiltrates (IGHM, CD3, CD8, FOXP3, CD68, CD205), chemokines (CXCL9, CXCL10, CXCL13) and invasion markers (MMP7, MMP9).

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2019
  2. Study start12 Jun 2019
  3. Primary completion27 Oct 2022
  4. Study completion2 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open-label, single-arm, multicenter phase II trial
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03841201
Sponsor's protocol ID
IMMUNIB
Status last verified
May 2023
First submitted
12 Feb 2019
Last updated
12 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib and Nivolumab in people with Advanced Hepatocellular Carcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) according to RECIST 1.1 (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03841201.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2023.

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