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

NCT02683941 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: A-US-52030-3282015-004992-62
• Study Type: interventional
• Target: 77
• Locations: 11 countries
• Sites: 57

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.

Conditions

Neuroendocrine Tumors in Lung

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review

  PFS for subjects randomised in the lanreotide group, assessed by central review using Response Evaluation Criteria In Solid Tumours Version 1.1 (RECIST v1.1) criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during either the double-blind phase, or the open-label treatment phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

  Up to a maximum of 33 months

Secondary Outcomes (9)

• Median PFS Time in the Double-Blind Phase, Assessed by Central Review

  Up to a maximum of 15 months

• Median PFS Time in the Double-Blind Phase, Assessed by Local Review

  Up to a maximum of 15 months

• Objective Response Rate (ORR) in the Double-Blind Phase

  Up to a maximum of 15 months

• Time to Treatment Failure (TTF) in the Double-Blind Phase

  Up to a maximum of 15 months

• Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase

  Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months)

Study Arms (2)

Lanreotide (Autogel formulation)

EXPERIMENTAL

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

Drug: Lanreotide (Autogel formulation); Drug: Best Supportive Care

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Best Supportive Care

Interventions

Lanreotide (Autogel formulation) DRUG

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

Also known as: Lanreotide Depot (US)

Lanreotide (Autogel formulation)

Placebo DRUG

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

Placebo

Best Supportive Care DRUG

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

Also known as: BSC

Lanreotide (Autogel formulation); Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ipsen: lead

Study Sites (57)

Arizona Oncology Associates

Tucson, Arizona, 85711, United States

Location

VA Greater Los Angeles

Los Angeles, California, 90073, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70112, United States

Location

Dana-Farber Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Center

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45237, United States

Location

Oregon Health and Science Center

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

Texas Oncology-Forth Worth

Fort Worth, Texas, 76104, United States

Location

AKH und Med. University Vienna Allg Krankenhaus Wien

Vienna, 1090, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, 4600, Austria

Location

Tom Baker Cancer Center

Calgary, Alberta, 2TN 4N2, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, S7N 4H4, Canada

Location

Cancer Care of Manitoba

Winnipeg, R3E0V9, Canada

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

NET-Centre, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Hôpital Edouard Herriot

Lyon, 69437, France

Location

CLLC, Institut Paoli Calmettes

Marseille, 13273, France

Location

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

Montpellier, 34000, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35033, France

Location

Centre René Gauducheau ICO institut de Cancerologie de l'Ouest

Saint-Herblain, 44805, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Zentralklinik Bad Berka GmbH

Bad Berka, 99437, Germany

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

Universitätsklinikum Essen (AöR)

Essen, 45145, Germany

Location

Johann Wolfgang Goethe-Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universita di Genova

Genova, 16132, Italy

Location

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

Meldola, 47014, Italy

Location

Azienda Ospedaliera Antonio Cardarelli

Napoli, 80131, Italy

Location

Azienda Ospedaliera Universitaria di Perugia Santa Maria della Misericordia

Perugia, 06123, Italy

Location

Insittuto Clinico Humanitas

Rozzano, 20089, Italy

Location

Antoni van Leeuwenhoek

Amsterdam, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Zakladu Medycyny Nuklearne i Endokrynologii Onkologicznej

Gliwice, 44-101, Poland

Location

University Center of Ophtalmology & Oncology

Katowice, 40-514, Poland

Location

Szpital Uniwersytecki W

Krakow, 31-501, Poland

Location

Szpital Kliniczny im. H. Święcickiego U.M.

Poznan, 60-355, Poland

Location

GAMMED

Warsaw, 02-348, Poland

Location

Hospital Universitari, Vall d'Hebron

Barcelona, 8035, Spain

Location

University Hospital Ramón y Cajal

Madrid, 28412, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Cancer Center, Beatson Oncology

Glasgow, G12 0YN, United Kingdom

Location

Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

Royal Free Hospital

London, NW3 2QC, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Interventions

lanreotide

Limitations and Caveats

The majority of subjects who entered the open-label treatment phase were withdrawn due to study termination by the sponsor.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: February 17, 2016
• Study Start: March 6, 2017
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: July 6, 2022
• Results First Posted: October 29, 2021

Record last verified: 2022-06

Locations

DK (2); CA (6); DE (4); NL (2); PL (5); ES (4); FR (7); GB (6); US (14); AU (2); IT (5)