Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumours

NCT ID: NCT02683941

Last Updated: 2022-07-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-06
• Study Completion Date: 2020-02-28

Brief Summary

This is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of LAN plus BSC versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical bronchopulmonary NETs.

This study contains two phases: the Double-Blind (DB) Phase, and the Open Label (OL) Phase. The DB Phase includes: Screening, Baseline and Treatment period. The OL Phase will consist of two periods: Treatment Period and Follow-Up Period.

The primary objective will be to describe the antitumour efficacy of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) every 28 days, in terms of progression-free survival (PFS), measured by central review using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, in subjects randomized to LAN with unresectable and/or metastatic well differentiated, typical or atypical bronchopulmonary neuroendocrine tumours.

Recent updates of National Cancer Institute Cancer Network (NCCN) & European Neuroendocrine Tumor Society (ENETS) guidelines recommend SSA in first line for the treatment of locoregional unresectable or metastatic bronchopulmonary NETs as an option beyond 'observation' leading to slow and difficult recruitment in SPINET study. Consequently, it was decided to prematurely stop the recruitment in the SPINET study and to transition all subjects still treated in the double-blind phase to the open label (OL) treatment and follow-up phases following respective country approvals of Amendment #5.

The new aim of this Phase 3, multicenter, prospective, randomized placebo-controlled clinical study is to describe the antitumor efficacy and safety of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) in subjects with well-differentiated, metastatic and/or unresectable, typical or atypical, bronchopulmonary NETs.

Detailed Description

As planned initially, a total of 216 eligible patients with well-differentiated typical or atypical, metastatic and/or unresectable bronchopulmonary NETs, and a positive somatostatin receptor imaging (SRI) (Octreoscan® ≥ grade 2 Krenning scale; Ga-PET scan: uptake greater than liver background), were to be randomized 2:1 to either LAN plus BSC (120mg/28 days) or placebo plus BSC following the stratification of 1) typical versus atypical and 2) prior chemotherapy versus no prior chemotherapy*.

• cytotoxic chemotherapy or molecular targeted therapy or interferon.

At the time of the premature stop of the recruitment (as per Protocol Amendment #5), 77 patients were enrolled. All patients still treated in the DB Phase were entered into the OL Phase (either for Follow up or for OL treatment periods). The transition to the OL periods was done on a country-basis and per patient, at the following planned scheduled visit (i.e. approximately 28 days from the last injection). Patients enrolled into the study not progressing at the time of study stop, and who agree to stay on LAN therapy (i.e. OL Treatment Period) receive the study active treatment until evidence of disease progression (based on local radiological assessment then confirmed centrally), development of unacceptable toxicity, or premature withdrawal for any reason or up a maximum of 18 months after the last patient randomized. After disease progression patients are followed for survival, QoL and all subsequent anticancer treatments in the OL Follow-up period up to the end of the study (i.e up to 18 months after the last patient randomized).

Conditions

Neuroendocrine Tumors in Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lanreotide (Autogel formulation)

120mg every 28 days until disease progression, death, or unacceptable toxicity

Group Type: EXPERIMENTAL

Lanreotide (Autogel formulation)

Intervention Type: DRUG

120mg every 28 days until disease progression, death, or unacceptable toxicity

Best Supportive Care

Intervention Type: DRUG

Best Supportive Care is best available therapy at the choice of the investigator

Placebo

120mg every 28 days until disease progression, death, or unacceptable toxicity during the double-blind phase. The patient may enter open-label phase for treatment with Lanreotide.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Saline solution 0.9% administered via deep subcutaneous injection every 28 days until disease progression.

Best Supportive Care

Intervention Type: DRUG

Best Supportive Care is best available therapy at the choice of the investigator

Interventions

Lanreotide (Autogel formulation)

120mg every 28 days until disease progression, death, or unacceptable toxicity

Intervention Type: DRUG

Placebo

Saline solution 0.9% administered via deep subcutaneous injection every 28 days until disease progression.

Intervention Type: DRUG

Best Supportive Care

Best Supportive Care is best available therapy at the choice of the investigator

Intervention Type: DRUG

Other Intervention Names

Lanreotide Depot (US); BSC

Eligibility Criteria

Inclusion Criteria

• Have metastatic and/or unresectable pathologically confirmed well-differentiated, typical or atypical neuroendocrine tumor of the bronchopulmonary
• Histologic evidence of Well differentiated Neuroendocrine tumors (NETs) of the bronchopulmonary (typical and atypical according to the World Health Organisation (WHO criteria), evaluated locally)
• Has a mitotic index <2 mitoses/2 mm2 for typical carcinoid (TC) and <10 mitoses/2 mm2 and/or foci of necrosis for atypical carcinoid (AC)
• At least one measurable lesion of the disease on imaging (CT or MRI; RECIST 1.1)
• Positive Somatostatin receptors (SSTR) imaging

Exclusion Criteria

• Poorly differentiated or high grade carcinoma, or patients with neuroendocrine tumors not of bronchopulmonary origin
• Has been treated with a Somatostatin analog (SSA) at any time prior to randomization, except if that treatment was for less than 15 days (e.g. peri-operatively) of short acting SSA or one dose of long acting SSA and the treatment was received more than 6 weeks prior to randomization
• Has been treated with Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization
• Has been treated with more than two lines of cytotoxic chemotherapy or molecular targeted therapy or interferon for bronchopulmonary NET

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

Arizona Oncology Associates

Tucson, Arizona, United States

VA Greater Los Angeles

Los Angeles, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

Ochsner Medical Center

New Orleans, Louisiana, United States

Dana-Farber Institute

Boston, Massachusetts, United States

Karmanos Cancer Center

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Roswell Park Cancer Center

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Oregon Health and Science Center

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Texas Oncology

Dallas, Texas, United States

Texas Oncology-Forth Worth

Fort Worth, Texas, United States

AKH und Med. University Vienna Allg Krankenhaus Wien

Vienna, , Austria

Klinikum Wels-Grieskirchen GmbH

Wels, , Austria

Tom Baker Cancer Center

Calgary, Alberta, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

McGill University Health Center

Montreal, Quebec, Canada

Saskatoon Cancer Centre

Saskatoon, , Canada

Cancer Care of Manitoba

Winnipeg, , Canada

Aarhus University Hospital

Aarhus, , Denmark

NET-Centre, Rigshospitalet

Copenhagen, , Denmark

Centre Oscar Lambret

Lille, , France

Hôpital Edouard Herriot

Lyon, , France

CLLC, Institut Paoli Calmettes

Marseille, , France

Institut du Cancer de Montpellier (ICM) Val d'Aurelle

Montpellier, , France

CHU de Rennes - Hôpital Pontchaillou

Rennes, , France

Centre René Gauducheau ICO institut de Cancerologie de l'Ouest

Saint-Herblain, , France

Institut Gustave Roussy

Villejuif, , France

Zentralklinik Bad Berka GmbH

Bad Berka, , Germany

Evangelische Lungenklinik Berlin

Berlin, , Germany

Universitätsklinikum Essen (AöR)

Essen, , Germany

Johann Wolfgang Goethe-Universitätsklinikum Frankfurt

Frankfurt, , Germany

Universita di Genova

Genova, , Italy

Insituti Scientifico Romagnolo per lo Studio e la cura dei Tumori (IRST)

Meldola, , Italy

Azienda Ospedaliera Antonio Cardarelli

Napoli, , Italy

Azienda Ospedaliera Universitaria di Perugia Santa Maria della Misericordia

Perugia, , Italy

Insittuto Clinico Humanitas

Rozzano, , Italy

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Zakladu Medycyny Nuklearne i Endokrynologii Onkologicznej

Gliwice, , Poland

University Center of Ophtalmology & Oncology

Katowice, , Poland

Szpital Uniwersytecki W

Krakow, , Poland

Szpital Kliniczny im. H. Święcickiego U.M.

Poznan, , Poland

GAMMED

Warsaw, , Poland

Hospital Universitari, Vall d'Hebron

Barcelona, , Spain

University Hospital Ramón y Cajal

Madrid, , Spain

Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Cancer Center, Beatson Oncology

Glasgow, , United Kingdom

Royal Surrey County Hospital

Guildford, , United Kingdom

Royal Free Hospital

London, , United Kingdom

King's College Hospital

London, , United Kingdom

Christie Hospital

Manchester, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Countries

United States; Austria; Canada; Denmark; France; Germany; Italy; Netherlands; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004992-62

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

A-US-52030-328

Identifier Type: -

Identifier Source: org_study_id