Study of the benefit of lenvatinib treatment in waiting list of liver transplantation after TACE failure in patients with hepatocellular carcinoma (HCC) : Ta-Len-Tra

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Oct 2024 → 15 Oct 2024

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

EISAI

External identifiers

EU CT number

2024-516408-40-00

EudraCT number

2022-000998-31

ClinicalTrials.gov

NCT05901194

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To estimate the proportion of LT among patients under lenvatinib with no complete response after 2 TACE

Secondary objectives 7

1. To estimate time to progression under lenvatinib and until LT
2. To compare progression rate under lenvatinib and until LT with the theorical proportion of 20%
3. To estimate the response rate by imaging before LT
4. To estimate the response rate by liver specimen pathology after LT
5. To estimate the recurrence rate after LT
6. To demonstrate the safety of this sequential strategy
7. Characterization of immune cell population of peripheral change under treatment

Conditions and MedDRA coding

Non-resectable hepatocellular carcinoma (HCC)

Regulatory references

Plan to share IPD

Yes

IPD plan description

All of the individual participant data collected during the trial, subject to compliance to regulations, will be available. Document (Study protocol, statistical analysis plan, informed consent form, clinical study report, analytic code) will be also available. Data will be available immediately following publication ending 2 years after publication, with investigators whose proposed use of the data has been approved by the PI and / or the review commitee if relevant. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patient presenting with non resectable HCC
2. Initial French AFP score < or = 2
3. Registered on national waiting list for LT
4. Who underwent TACE as a bridge to LT (i.e. persistent active disease, including stable disease or partial response or progression)
5. With no complete response after 2 TACE (i.e. persistent active disease, including stable disease or partial response or progression)
6. Non eligible for percutaneous ablation
7. Informed, written consent obtained from the patient
8. Having the rights to French social insurance
9. Aged of 18 years or older
10. Adequate bone marrow, liver and renal function as assessed by the following laboratory tests: - Hemoglobin > 8.5 g/dL - Absolute neutrophil count ≥ 1500/mm3 (≥ 1200/mm3 for black/African, American) - Platelet count ≥ 60,000/ mm3 - Total bilirubin ≤ 2 mg/dL or 34 mcmol/l - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) - Serum creatinine ≤ 1.5 x ULN - Prothrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 50 % - Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
11. Patient with QT/QTc < 480 ms
12. Women of childbearing potential (WOCBP) need to accept one effective method of contraception until 1 month after the last lenvatinib intake and avoid pregnancy
13. Patients who are sexually active with WOCBP partners need to accept one effective method of contraception until 1 month after lenvatinib intake and men must agree to use adequate contraception

Exclusion criteria 15

1. Contraindication of lenvatinib and excipient: 1) Cardiovascular: - Rhythmic or ischemic recent or uncontrolled cardiac disease: Pacemakers or patients who have a history of cardiac arrhythmias or irregular heartbeats (in case of electroporation procedure) - Congestive heart failure New York Heart Association (NYHA) ≥ class 2 - Unstable angina or myocardial infarction within the past 6 months before enrolment - Uncontrolled arterial hypertension (systolic ≥ 140 mmHg, diastolic ≥ 90 mmHg) 2) Ongoing ascites: Refractory ascites according to EASL guidelines definition (ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment) 3) Coagulopathy 4) Ongoing infection > Grade 2 according to NCI-current CTCAE . Hepatitis B is allowed if no active replication is present (below 100 IU/mL). Hepatitis C is allowed if no antiviral treatment is ongoing
2. Known hypersensitivity to the study drug or excipients in the formulation
3. Decompensated cirrhosis (Child-Pugh > A6)
4. Prior systemic therapy with oral TKI and/or immunotherapy
5. Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumours. Any cancer curatively treated > 3 years prior to study entry is permitted
6. Recent digestive bleeding associated with portal hypertension (whithin the 3 months prior to inclusion in the study)
7. Advanced or Metastatic HCC (BCLC C)
8. Persistent proteinuria of NCI-current CTCAE ≥ Grade ≥ Grade 3
9. Project of living donor
10. Pregnant or lactating woman
11. Curator or guardianship or patient placed under judicial protection
12. Participation in other interventional research during the study
13. History within the past 3 months before enrollment of haemorrhage, gastrointestinal perforation, gastrointestinal or non-gastrointestinal fistula
14. History of aneurism
15. Hypokalemia, hypomagnesemia and hypocalcemia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients with TACE failure and treated with lenvatinib who have a LT

Secondary endpoints 7

1. Time to progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST.
2. Progression under lenvatinib before LT by imaging. Progression will be based on RECIST and mRECIST.
3. Response rate before LT by imaging
4. Response rate by liver specimen pathology after the LT
5. Recurrence rate after LT by imaging
6. Evaluate Safety by AE and SAE (using current CTCAE)
7. The endpoints associated to the immunophenotyping of peripheral blood immune cell population will be on the ancillary analyses.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Olivier ROSMORDUC

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Olivier ROSMORDUC

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications