Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours (CLARINET)

Phase III, Randomised, Double-blind, Stratified Comparative, Placebo Controlled, Parallel Group, Multi-centre Study to Assess the Effect of Deep Subcutaneous Injections of Lanreotide Autogel 120mg Administered Every 28 Days on Tumour Progression Free Survival in Patients With Non-functioning Entero-pancreatic Endocrine Tumour

The study will compare the difference between lanreotide Autogel and placebo on progression free survival in patients who have an endocrine tumour in the pancreas or intestines.

Study Overview

• Status: Completed
• Conditions: Endocrine Tumors
• Intervention / Treatment: Drug: lanreotide (Autogel formulation); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • University Hospital
• Belgium
  • Antwerpen, Belgium
    • UZ Antwerpen
  • Bruxelles, Belgium
    • UCL Saint Luc
  • Gent, Belgium
    • UZ Gent
• Czechia
  • Olomouc, Czechia
    • Fekultni nemocnice Olomouc
  • Praha, Czechia
    • General faculty
  • Prague
    • Bulovce, Prague, Czechia
      • Fakultni nemocnice Na
• Denmark
  • Aarhus, Denmark
    • Sygehus Hospital
  • Copenhagen, Denmark
    • Rigshospitalet
• France
  • Boulogne Billancourt, France, 92100
    • Hôpital A. Paré
  • Clichy, France, 92118
    • Hôpital Beaujon
  • Lille, France, 59020
    • CAC Oscar Lambret
  • Lyon, France, 69437
    • Hôpital Edouard Herriot
  • Marseille, France, 13385
    • CHU La Timone
  • Reims, France, 51092
    • Hôpital R. Debré
  • St Raphael, France, 83300
    • CHI Fréjus St Raphaël
  • Toulouse, France, 31059
    • Hôpital Rangueil
  • Villejuif, France, 94805
    • Unité de gastro enterologie IGR
• Germany
  • Berlin, Germany
    • Charite Hospital
  • Erlangen, Germany
    • University Hospital
  • Lubeck, Germany
    • University Hospital
  • Mainz, Germany
    • Gutenberg University Hospital
  • Munchen, Germany
    • University Hospital
  • Neuss, Germany
    • Lukas Hospital
• India
  • Hyderabad, India
    • Global Hospital
  • Mumbai, India
    • Tata Memorial Hospital
• Italy
  • Aviano, Italy
    • Centro di Refierimiento Oncologica
  • Bologna, Italy
    • Azienda Malpighi
  • Milano, Italy
    • INSCT
  • Naples, Italy
    • University of Naples
  • Pisa, Italy
    • Hospital S. Chiara
  • Torino, Italy
    • Azienda San Giovanni Battista
• Netherlands
  • Gronigen, Netherlands
    • UMC Gronigen
  • Rotterdam, Netherlands
    • Erasmu MC
  • Utrecht, Netherlands
    • UMC Utrecht
• Poland
  • Gliwice, Poland
    • Centrum Onkologii-Instytut im. Marii Sklodowskiej - Curie, oddzial w Gliwicach, Zaklad Medycyny Nuklearnej i Endokrynologii Onkologicznej ul.
  • Poznan, Poland
    • Katedra i Klinika Endokrynologii Przemiany Materii i Chorob Wewnetrznych Uniwersytetu Medycznego w Poznaniu
  • Warszawa, Poland
    • Samodzielny Publiczny Centralny Szpital Kliniczny, Katedra i Klinika Chorob Wewnetrznych I Endokrynologii ul. Banacha 1 a
  • Warszawa, Poland
    • Szpital Bielanski im. Ks. Jerzego Popieluszki, Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Klinika Endokrynologii Centrum Medycznego Ksztalcenia Podyplomowego
  • Warszawa, Poland
    • Zaklad Diagnosttyki Radiologicznej, Centralny Szpital Klincny, Ministrerstwa Spraw Wewnetrznych i Administratracji w Warzawie
  • Zabrze, Poland
    • Silesian Medical University
• Slovakia
  • Slovakia, Slovakia
    • Narodny onkologicky ustav, Bratislava
  • Slovakia, Slovakia
    • Vychodoslovensky onkologicky ustav, Rastislavova
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Institut Catala Oncologia
  • Madrid, Spain
    • Hospital La Paz
  • Madrid, Spain
    • Hospital G. Maranon
  • Tenerife, Spain
    • Hospital Nuestra Señora de La Candelaria
• Sweden
  • Goteborg, Sweden
    • Sahlgrenska Hospital
  • Stockholm, Sweden
    • Karolinska University Hospital
  • Uppsala, Sweden
    • University Hospital
• United Kingdom
  • Basingstoke, United Kingdom
    • Basingstoke and North Hampshire Hospital
  • Belfast, United Kingdom
    • Royal Victoria Hospital
  • Cardiff, United Kingdom
    • University Hospital Wales
  • Edinburgh, United Kingdom
    • Western General Hospital
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom
    • St James Hospital
  • Leicester, United Kingdom
    • Leicester Royal Infirmary
  • London, United Kingdom
    • Royal Free Hospital
  • London, United Kingdom
    • St Bartholomew's Hospital
  • Nottingham, United Kingdom
    • QMC
  • Oxford, United Kingdom
    • Churchill Hospital
  • Sheffield, United Kingdom
    • Royal Hallamshire Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Outpatient Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21287-4606
      • The John Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-5666
      • University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Endocrine tumour in the intestine or pancreas and with locally advanced or metastatic disease
• No hormone related symptoms
• Well or moderately differentiated tumour confirmed by histology
• Tumour lesions which are measurable by a CT or MRI scan

Exclusion Criteria:

• Previously treated with a somatostatin analogue unless more than 6 months ago and given for no more than 15 days
• Treated within the last 6 months with interferon, chemoembolisation or chemotherapy or at any time with a radionuclide
• Had a previous cancer except basal cell carcinoma and/or in situ carcinoma of the cervix/uterus and/or patients treated with curative intent and free from disease for 5 years
• Pregnant or lactating
• Females must use adequate contraception during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Saline solution 0.9% administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks.
Experimental: lanreotide (Autogel formulation)	Drug: lanreotide (Autogel formulation); 120mg administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from randomization to first documentation of disease progression, or death. Disease progression centrally assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.0	From randomisation up to the last tumour assessment (scheduled at 96 weeks). Radiological scans were performed every 12 weeks during the first year and every 24 weeks during the second year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Alive & Without Disease Progression	Percentage of patients still ongoing (or completing at Week 96) without centrally assessed disease progression or death at Weeks 48 and 96.	Week 48 & 96
Pharmacokinetic Profile of Lanreotide	Pharmacokinetic Profile of Lanreotide assessed by mean serum concentration at specified timepoints	Week 4, 12, 24, 36, 48, 72, 96
Change in the Global Health Status Quality of Life Assessment	Transformed scores from European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire responses (QLQ)-C30. Questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life.	Week 12 to Week 96 (last visit)
Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels		Week 12 to Week 96 (last visit)
Percentage of Patients Still Alive Based on Available Overall Survival Data	Overall survival defined as the time from randomisation to death due to any cause. Subjects were followed for overall survival beyond study completion/withdrawal via annual telephone contact until the last subject completed the study.	Randomisation to death or last visit, up to 321 weeks

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Medical Director, Endocrinology, Ipsen

Publications and helpful links

General Publications

• Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlackova E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33. doi: 10.1056/NEJMoa1316158.
• Lybaert W, Van Hul E, Woestenborghs H. Long-term disease control of a pancreatic neuroendocrine tumor with lanreotide autogel((R)): a case report. Case Rep Oncol. 2014 Sep 26;7(3):673-80. doi: 10.1159/000368207. eCollection 2014 Sep.
• Caplin ME, Pavel M, Phan AT, Cwikla JB, Sedlackova E, Thanh XT, Wolin EM, Ruszniewski P; CLARINET Investigators. Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study. Endocrine. 2021 Feb;71(2):502-513. doi: 10.1007/s12020-020-02475-2. Epub 2020 Oct 14.

Helpful Links

• Lay language results summary

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: July 17, 2006
• First Submitted That Met QC Criteria: July 17, 2006
• First Posted (Estimated): July 18, 2006

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Non functioning entero-pancreatic tumours
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Antineoplastic Agents; Lanreotide
• Other Study ID Numbers: 2-55-52030-726; 2005-004904-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes