Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour (NET729)

Open Label Extension Study of Lanreotide Autogel 120 mg in Patients With Non-functioning Entero-pancreatic Endocrine Tumour

The primary purpose of this extension study was to assess the long term safety of patients with nonfunctioning enteropancreatic neuroendocrine tumour (NET), who were treated with open label lanreotide Autogel (120 mg every 28 days) and who participated in a previous study, 2-55-52030-726 (NCT00353496).

Study Overview

• Status: Completed
• Conditions: Non Functioning Entero-pancreatic Endocrine Tumour
• Intervention / Treatment: Drug: lanreotide (Autogel formulation)

Detailed Description

While somatostatin analogue treatment is the primary medical therapy for patients with hormone related symptoms and is indicated for the treatment of hormone related symptoms in many international countries, there is no reference standard medical therapy for asymptomatic patients. A 96-week study (Study 2-55-52030-726 (726), NCT00353496) was conducted to investigate the effect of lanreotide Autogel on progression free survival (PFS) in patients with well or moderately differentiated nonfunctioning enteropancreatic NET. While Study 726 was ongoing, the sponsor considered that therapy with lanreotide Autogel should continue to be an option to patients with stable disease at the end of the 96-week treatment period. This extension study was therefore initiated (Study 2-55-52030-729 (729)) which investigated the long term safety of treatment with lanreotide Autogel and enabled investigators to continue to treat their patients who had stable disease, as well as to treat placebo patients who experienced disease progression during the initial 96-week study (Study 726).

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
    • UZ Antwerpen
  • Bruxelles, Belgium
    • UCL Saint Luc
• Czechia
  • Prague, Czechia
    • Fakultni nemocnice Na Bulovce
  • Praha, Czechia
    • General faculty
• France
  • Clichy, France, 92118
    • Hopital Beaujon
  • Lille, France, 59020
    • CAC Oscar Lambret
  • Lyon, France, 69437
    • Hopital Edouard Herriot
  • Reims, France, 51092
    • Hopital R. Debre
• Italy
  • Aviano, Italy
    • Centro di Refierimiento Oncologica
  • Milano, Italy
    • INSCT
  • Naples, Italy
    • University of Naples
  • Torino, Italy
    • Azienda San Giovanni Battista
• Poland
  • Warszawa, Poland
    • Centrum Diagnostyczno-Lecznicze "Gammed"
  • Warszawa, Poland
    • Zaklad Diagnosttyki Radiologicznej, Centralny Szpital Klincny
• Slovakia
  • Bratislava, Slovakia
    • Národný onkologický ústav
• Spain
  • Barcelona, Spain
    • Hospital Vall D'Hebron
  • Barcelona, Spain
    • Institut Catala Oncologia
• United Kingdom
  • 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
  • London, United Kingdom
    • Royal Free Hospital
  • Nottingham, United Kingdom
    • QMC
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Outpatient Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287-4606
      • The Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Had provided written informed consent prior to any study-related procedures.

2. Had been enrolled and treated in Study 2-55-52030-726 and either:

   • Was stable at 96 weeks of treatment (whatever the treatment received during the 2 years of participation, i.e. no code break at Week 96); or,
   • Had received at least one injection in Study 2-55-52030-726 and had disease progression, confirmed by central assessment, during the course of the study and code break showed placebo.
3. Had a World Health Organisation (WHO) performance score lower than or equal to 2.

Exclusion Criteria:

1. Had been enrolled and treated in the frame of the protocol and had disease progression during the study and the code break showed a treatment with lanreotide Autogel 120 mg.
2. Had received any new treatment for the entero-pancreatic NET since the end of participation in the study.
3. Were likely to require any additional concomitant treatment to lanreotide Autogel 120 mg for the entero-pancreatic NET.
4. Had been treated with radionuclide at any time prior to study entry.
5. Had a history of hypersensitivity to drugs with a similar chemical structure to lanreotide Autogel 120 mg.
6. Were likely to require treatment during the study with drugs that were not permitted by the study protocol.
7. Were at risk of pregnancy or lactation. Females of childbearing potential had to provide a negative pregnancy test at the start of study and had to be using oral, double barrier or injectable contraception. Non-childbearing potential was defined as postmenopause for at least 1 year, or surgical sterilisation or hysterectomy at least 3 months before the start of the study.
8. Had any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
9. Had abnormal findings at Visit 1, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might have jeopardised the patient's safety or decreased the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
10. Previous enrolment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Lanreotide (Autogel formulation); Patients from the preceding DB study (Study 726) were treated with open label lanreotide Autogel 120 mg by deep subcutaneous injections every 28 days. Patients were included if they had been treated with lanreotide (Autogel formulation) or placebo in DB Study 726 and had stable disease at the end of the 96-week treatment period, or if they had received placebo and had disease progression at any time during Study 726. Safety data were based on the safety population patients who received lanreotide in Study 729). The main efficacy analysis was based on the ITT population (patients randomised in Study 726 regardless of whether they continued into Study 729).

Drug: lanreotide (Autogel formulation); Autogel 120 mg; Other Names: Somatuline Depot; Somatuline; Somatuline Autogel; Lanreotide Autogel; Lanreotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse events (AEs) that were ongoing from Study 726 at the time of entry into Study 729 were transcribed into the case report form (CRF) for Study 729 with a start date corresponding to the original report of this AE in Study 726. All new AEs that started after the last visit in Study 726 (i.e. irrespective of whether the AE had onset before or after giving informed consent for Study 729) were recorded Study 729. An AE was considered as a treatment emergent adverse event (TEAE) for Study 729 if: It was not present prior to receiving the first dose of study treatment in Study 729; or,; It was present prior to receiving the first dose of study treatment in Study 729 but the intensity increased after the first dose of study treatment in Study 729. Adverse event data are presented in the AE section.	Throughout the study until the completion/early discontinuation visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS): Kaplan-Meier Estimate	The time from randomisation in Study 726 to the first occurrence of either disease progression (measured using Response Evaluation Criteria In Solid Tumours [RECIST] criteria) or death in Study 726 or in Study 729, or equivalently, the Progression Free Survival (PFS) time. Tumour assessments for the placebo group after switching to open label lanreotide Autogel were excluded for the purpose of this analysis. Estimation of the median was based on the Kaplan-Meier method.	Throughout the study (every 24 weeks and at completion/withdrawal visit)

Collaborators and Investigators

• Sponsor: 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, Gomez-Panzani E, Ruszniewski P; CLARINET Investigators. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016 Mar;23(3):191-9. doi: 10.1530/ERC-15-0490. Epub 2016 Jan 7.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: February 11, 2009
• First Submitted That Met QC Criteria: February 11, 2009
• First Posted (ESTIMATE): February 12, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Neuroendocrine tumour; Lanreotide; NET; Somatuline
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Pancreatic Diseases; Adenoma; Pancreatic Neoplasms; Endocrine Gland Neoplasms; Adenoma, Islet Cell; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Lanreotide; Somatostatin
• Other Study ID Numbers: 2-55-52030-729; 2008-004019-36 (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/).