Lenvatinib Efficacy in Metastatic Neuroendocrine Tumors

NCT02678780 | Completed Phase 2 Results

• 2 other identifiers: GETNE15092015-001467-39
• Study Type: interventional
• Target: 123
• Locations: 4 countries
• Sites: 22

Brief Summary

This is a prospective, international, multi-center, open label, stratified, exploratory phase II study evaluating the efficacy and safety of lenvatinib in patients with advanced/metastatic, neuroendocrine tumors of the pancreas after progression to a previous targeted agent (cohort A) or gastrointestinal tract after progression to somatostatin analogues (cohort B).

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (2)

• Best Response Rate by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Upon Central Radiologic Assessment

  Data cut-off for the primary study analysis will happen following after the last patient included in the study has performed the second tumor evaluation (week 18 after first dose of study drug as first evaluation will take place 6 weeks after first dose, following tumor assessment will take place every 12 weeks until documentation of disease progression or start of another anticancer therapy. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions: Complete Response (CR)= Disappearance of all target lesions; Partial Response (PR)= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD)=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; Stable Disease (SD)= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR) = CR + PR.

  Up to 18 months

• Overall Response Rate (ORR) by RECIST v 1.1 Upon Central Radiologic Assessment

  Data cut-off for the primary study analysis will happen following after th e last patient included in the study has performed the second tumor evaluation (week 18 after first dose of study drug as first evaluation will take place 6 weeks after first dose, following tumor assessment will take place every 12 weeks until documentation of disease progression or start of another anticancer therapy

  Up to 18 months

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  Up to 18 months

• Number of Participants With Early Tumor Shrinkage (ETS)

  Up to 18 months

• Deepness of Response (DpR)

  Up to 18 months

• Tumour Shrinkage

  18 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Patients with advanced/metastatic, histologically confirmed, grade 1/2 (G1/G2) of 2010 WHO (World Health Organization) classification neuroendocrine tumors of the pancreas after progression to a previous targeted agent. Treatment: Dosing schedule of 24 mg once a day of Lenvatinib (two 10-mg capsules + one 4-mg capsule)

Drug: Lenvatinib

Cohort B

EXPERIMENTAL

Patients with advanced/metastatic, histologically confirmed, grade 1/2 (G1/G2) of 2010 WHO (World Health Organization) classification neuroendocrine tumors of gastrointestinal tract after progression to somatostatin analogues Treatment: Dosing schedule of 24 mg once a day of Lenvatinib (two 10-mg capsules + one 4-mg capsule)

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Also known as: LENVIMA™

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all of the following criteria to be included in this study:
• Subjects must have histologically confirmed diagnosis of one of the following advanced/metastatic neuroendocrine tumor types:
• WHO Classification G1/G2 (Ki67\<20% and mitotic count ≤20 mitoses x 10 HPF) pancreatic neuroendocrine tumor
• WHO Classification G1/G2 (Ki67\<20% and mitotic count ≤20 mitoses x 10 HPF) gastrointestinal neuroendocrine tumor (including stomach, small intestine and colorectal origins).
• Subjects must have evidence of measurable disease meeting the following criteria:
• At least 1 lesion of ≥ 1.0 cm in the longest diameter for a non-lymph node, or ≥ 1.5 cm in the short-axis diameter for a lymph node, which is serially measurable according to RECIST 1.1 (Appendix I) using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of ≥ 1.5 cm.
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation or liver embolization must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
• Subjects must show evidence of disease progression by radiologic image techniques within 12 months (an additional month will be allowed to accommodate actual dates of performance of scans, i.e., within ≤ 13 months) prior to signing informed consent, according to RECIST 1.1 (Appendix I)
• Pancreatic origin: progression after a previous targeted agent (including mTOR inhibitors, such as everolimus or antiangiogenic therapies, such as sunitinib, sorafenib, axitinib, bevacizumab within others). Combination therapies in the same treatment line (such as sorafenib plus bevacizumab, chemotherapy plus antiangiogenic drugs) are considered one treatment line and are allowed to be included in the study. Patients must be treated with only one previous line of targeted agent(s)-based therapy.
• Previous therapy with somatostatin analogues and/or interferon is allowed and is not considered as a previous targeted agent therapy.
• Gastrointestinal origin: progression after therapy with antitumoral doses of somatostatin analogs (octreotide LAR 30 mg every 28 days or Lanreotide 120 mg every 28 days) and/or interferon treatment.
• Only for patients with pancreatic origin neuroendocrine tumors, one previous line with chemotherapy is allowed.
• Concomitant somatostatin analogues are allowed in both cohorts during the study.
• Patients with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for at least one month.
• All prior chemotherapy or radiation-related toxicities must have resolved to \< Grade 2 (following CTCAE V 4.03 grade levels), except alopecia and infertility.

You may not qualify if:

• WHO Classification G3 neuroendocrine tumors of the pancreas and gastrointestinal tract.
• Two or more prior lines of targeted agents-based therapy in pancreatic origin and any previous line of targeted therapy for gastrointestinal origin or any ongoing antiproliferative treatment for advanced/metastatic neuroendocrine tumors, with the exception of somatostatin analogues therapy.
• More than one previous line of chemotherapy in pancreatic neuroendocrine tumors.
• Previous chemotherapy in gastrointestinal neuroendocrine tumors.
• Prior treatment with lenvatinib.
• Subjects who have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. This does not apply to the use of somatostatin analogues for symptomatic therapy.
• Major surgery within 3 weeks prior to the first dose of study drug.
• Subjects having \> 1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24h will be ineligible.
• Gastrointestinal malabsorption, or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina; myocardial infarction or stroke within 6 months prior to the first dose of study drug, or cardiac arrhythmia requiring medical treatment. The left ventricular ejection fraction in the echocardiogram must be of at least 50%.
• Prolongation of QTcF interval to \> 480 msec.
• Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. Treatment with low molecular weight heparin (LMWH) is allowed.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Active infection (any infection requiring treatment).
• Active malignancy within the past 5 years (except for definitely treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix).

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• Eisai Limited: collaborator
• Experior S.L.: collaborator

Study Sites (22)

Universitätsklinik für Innere Medizin

Graz, 8036, Austria

Location

Medizinische Universität Wien

Vienna, a-1090, Austria

Location

Spedali Civili di Brescia

Brescia, Italy

Location

Instituto Oncologico Mediterraneo

Catania, Italy

Location

Azienda Ospedaliero Universitaria Careggi - SC di Oncologia

Florence, 50139, Italy

Location

IRST of Meldola

Meldola, Italy

Location

Istituto Europeo di Oncologia - Unità di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini

Milan, 20141, Italy

Location

AOU Policlinico di Modena - DH Oncologico

Modena, 41124, Italy

Location

IRCCS Napoli

Napoli, Italy

Location

Hospital Universatorio de Verona

Verona, Italy

Location

Hospital Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

Location

Hospital de Donostia

Donostia / San Sebastian, Basque Country, Spain

Location

Hospital Marqués de Valdecilla

Santander, Cantabria, 39011, Spain

Location

Hospital Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital Universitario Vall Hebrón

Barcelona, 08035, Spain

Location

ICO Hospitalet

L'Hospitalet de Llobregat, 08908, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Beatson Oncology Centre Gartnavel General Hospital

Glasgow, G12 0YN, United Kingdom

Location

Christie Hospital, Manchester

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• Ligero M, Hernando J, Delgado E, Garcia-Ruiz A, Merino-Casabiel X, Ibrahim T, Fazio N, Lopez C, Teule A, Valle JW, Tafuto S, Custodio A, Reed N, Raderer M, Grande E, Garcia-Carbonero R, Jimenez-Fonseca P, Garcia-Alvarez A, Escobar M, Casanovas O, Capdevila J, Perez-Lopez R. Radiomics and outcome prediction to antiangiogenic treatment in advanced gastroenteropancreatic neuroendocrine tumours: findings from the phase II TALENT trial. BJC Rep. 2023 Aug 2;1(1):9. doi: 10.1038/s44276-023-00010-0.

  PMID: 39516643 DERIVED

• Capdevila J, Fazio N, Lopez C, Teule A, Valle JW, Tafuto S, Custodio A, Reed N, Raderer M, Grande E, Garcia-Carbonero R, Jimenez-Fonseca P, Hernando J, Bongiovanni A, Spada F, Alonso V, Antonuzzo L, Spallanzani A, Berruti A, La Casta A, Sevilla I, Kump P, Giuffrida D, Merino X, Trejo L, Gajate P, Matos I, Lamarca A, Ibrahim T. Lenvatinib in Patients With Advanced Grade 1/2 Pancreatic and Gastrointestinal Neuroendocrine Tumors: Results of the Phase II TALENT Trial (GETNE1509). J Clin Oncol. 2021 Jul 10;39(20):2304-2312. doi: 10.1200/JCO.20.03368. Epub 2021 May 4.

  PMID: 33945297 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Start Up Unit
• Organization: Kapadi

maria.rocasalbas@kapadi.com

+34961452190

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2016
• First Posted: February 10, 2016
• Study Start: October 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: August 1, 2020
• Last Updated: July 24, 2025
• Results First Posted: July 24, 2025

Record last verified: 2025-07

Locations

AU (2); IT (8); ES (10); GB (2)