Clinical trial NCT02683941: Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumours
Official title: A Phase 3, Prospective, Randomized, Double-blind, Multi-center Study of the Efficacy and Safety of Lanreotide Autogel®/Depot 120 mg Plus BSC vs. Placebo Plus BSC for Tumour Control in Subjects With Well Differentiated, Metastatic and/or Unresectable, Typical or Atypical, Lung Neuroendocrine Tumours
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neuroendocrine Tumors in Lung
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2016-02-17
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: 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
timeFrame: Up to a maximum of 33 months
Secondary outcomes:
measure: Median PFS Time in the Double-Blind Phase, Assessed by Central Review
timeFrame: Up to a maximum of 15 months
measure: Median PFS Time in the Double-Blind Phase, Assessed by Local Review
timeFrame: Up to a maximum of 15 months
measure: Objective Response Rate (ORR) in the Double-Blind Phase
timeFrame: Up to a maximum of 15 months
measure: Time to Treatment Failure (TTF) in the Double-Blind Phase
timeFrame: Up to a maximum of 15 months
measure: Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase
timeFrame: 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)
measure: Percentage of Subjects With a Decrease of CgA ≥30% From Baseline at Week 8 in the Double-Blind Phase and Open-Label Treatment Phase
timeFrame: Baseline and Week 8 in the double-blind phase; Baseline and Week 8 in the open-label treatment phase
measure: Mean Changes From Baseline in Quality of Life (QoL), as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Global Health Status/QoL Score
timeFrame: Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)
measure: Percentage of Subjects Who Experienced QoL Deterioration
timeFrame: Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)
measure: Mean Changes From Baseline in Urinary 5-hydroxyindoleacetic Acid (5-HIAA) Levels in the Double-Blind Phase and Open-Label Treatment Phase
timeFrame: 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)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Los Angeles
country: United States
facility: VA Greater Los Angeles
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Dana-Farber Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Forth Worth
state: Texas
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: AKH und Med. University Vienna Allg Krankenhaus Wien
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
city: Winnipeg
country: Canada
facility: Cancer Care of Manitoba
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: NET-Centre, Rigshospitalet
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: CLLC, Institut Paoli Calmettes
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier (ICM) Val d'Aurelle
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Saint-Herblain
country: France
facility: Centre René Gauducheau ICO institut de Cancerologie de l'Ouest
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Essen
country: Germany
facility: Universitätsklinikum Essen (AöR)
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe-Universitätsklinikum Frankfurt
city: Genova
country: Italy
facility: Universita di Genova
city: Meldola
country: Italy
facility: Insituti Scientifico Romagnolo per lo Studio e la cura dei Tumori (IRST)
city: Napoli
country: Italy
facility: Azienda Ospedaliera Antonio Cardarelli
city: Perugia
country: Italy
facility: Azienda Ospedaliera Universitaria di Perugia Santa Maria della Misericordia
city: Rozzano
country: Italy
facility: Insittuto Clinico Humanitas
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Gliwice
country: Poland
facility: Zakladu Medycyny Nuklearne i Endokrynologii Onkologicznej
city: Katowice
country: Poland
facility: University Center of Ophtalmology & Oncology
city: Krakow
country: Poland
facility: Szpital Uniwersytecki W
city: Poznan
country: Poland
facility: Szpital Kliniczny im. H. Święcickiego U.M.
city: Warszawa
country: Poland
facility: GAMMED
city: Barcelona
country: Spain
facility: Hospital Universitari, Vall d'Hebron
city: Madrid
country: Spain
facility: University Hospital Ramón y Cajal
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Glasgow
country: United Kingdom
facility: Cancer Center, Beatson Oncology
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: