A Study Evaluating Lanreotide as Maintenance Therapy in Patients With Non-Resectable Duodeno-Pancreatic Neuroendocrine Tumors (REMINET) (REMINET)

A EUROPEAN, MULTICENTRE, PHASE II/III RANDOMISED DOUBLE-BLIND, PLACEBO CONTROLLED STUDY EVALUATING LANREOTIDE AS MAINTENANCE THERAPY IN PATIENTS WITH NON-RESECTABLE DUODENO-PANCREATIC NEUROENDOCRINE TUMOURS AFTER FIRST-LINE TREATMENT

This European, prospective, multicentre, double-blind randomised study will evaluate the effect of lanreotide (120 mg every 28 days until disease progression) versus placebo in patients with metastatic/locally advanced, non-resectable, duodeno-pancreatic neuroendocrine tumours.

Study Overview

• Status: Terminated
• Conditions: Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours
• Intervention / Treatment: Drug: Placebo; Drug: lanreotide

Detailed Description

This is a European, prospective, multicentre, double-blind randomised study evaluating lanreotide (120 mg every 28 days until disease progression) versus placebo in patients with metastatic/locally advanced, non-resectable, duodeno-pancreatic neuroendocrine tumours.

Depending on the phase II results, the study may be continued into phase III. The treatment and follow-up of patients will be the same in phase II and phase III.

After the first-line treatment, patients will be randomly assigned with a 1:1 ratio to receive either lanreotide or placebo. The study treatment should be initiated within 6 weeks following the confirmation date of stable disease or objective response.

Treatment period:

For each patient, the investigational products (lanreotide or placebo) will be provided according to a double-blind procedure until disease progression or toxicity, in accordance with the protocol.

The estimated average treatment duration for all patients is 12 months.

Follow-up period:

To evaluate overall survival, patients in phase II will have a minimum follow-up period of 12 months; if the study continues to phase III, these patients will have a maximum follow-up period of 10 years. Phase III patients will have a minimum follow-up period of 5 years.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Clinique Universitaire Saint-Luc
• France
  • Angers, France
    • CHU d'Angers - Hôtel Dieu
  • Bobigny, France
    • CHU - Hôpital Avicenne
  • Caen, France
    • CHU Côte de Nacre
  • Clermont Ferrand, France
    • CHU Estaing
  • Clichy, France
    • Hopital Beaujon
  • Dijon Cedex, France, 21079
    • CHU Le Bocage Service d'HGE
  • La Roche Sur Yon, France
    • CH Les Oudairies
  • Lyon, France
    • Hôpital Edouard Herriot
  • Marseille, France
    • CHU La Timone
  • Orléans, France
    • Hôpital de la Source
  • Paris, France
    • CHU Cochin
  • Pessac, France
    • Hôpital Haut Lévêque Bat Magellan, Service d'hépato-gastroentérologie
  • Poitiers, France
    • Hopital de la Milétrie
  • Reims, France
    • Hôpital Robert Debré
  • Rennes, France
    • CHU de Rennes - Hopital Pontchaillou
  • Rouen, France
    • CHU Charles Nicolle
  • Saint Priest En Jarez, France
    • CHU de Saint Etienne
  • Toulouse, France
    • Hopital Rangueil
  • Villejuif, France
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany
    • Charite Campus Virchow Kilikum
  • Marburg, Germany
    • University Hospital Marburg
• United Kingdom
  • London, United Kingdom
    • Royal Free Hospital Neuroendocrine Tumour Unit
  • Manchester, United Kingdom
    • Manchester Academic Health Sciences Centre (MAHSC)

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:

• Metastatic (synchronous or metachronous) or locally advanced, non-resectable, well-differentiated duodeno-pancreatic neuroendocrine tumour, of grade 1 or 2 (WHO 2010 classification; Ki-67 ≤ 20%)
• Progressive before first-line treatment
• Histologically confirmed (either on primary tumour or metastases)
• Pathological diagnosis validated by the NET consulting pathologist
• Documented stable disease or objective response after first-line treatment, within 4 weeks (28 days) prior to randomisation
• The first-line treatment will consist of either a chemotherapy or biotherapy (everolimus or sunitinib) as referred to TNCD or ENETS guidelines. Treatment must have been administered for 3 to 6 months for chemotherapy and for 6 months for biotherapy
• Non-functional tumour or gastrinoma controlled by PPIs
• Age > or = 18 years
• WHO 0, 1 or 2
• Effective contraception for male or female patients of childbearing age, defined as: oral contraceptives, intra-uterine devices, barrier contraceptive methods along with a spermicide gel, or surgical sterilisation. Female patients should use this contraception throughout the treatment period and for 6 months after the last treatment administration. Male patients should use contraception throughout the treatment period and for 3 months after the last treatment administration.
• Signed informed consent prior to initiation of any study-specific procedures or treatment.

Exclusion Criteria:

• History of haematological malignancy or other cancer, except those treated for more than 5 years and considered as cured, carcinoma in situ of the cervix and treated skin cancer (excluding melanoma)
• Poorly differentiated neuroendocrine carcinoma or NET grade 3 ENETS (Ki-67 > 20%)
• If primary resected, bone metastasis exclusively
• Pre-treatment by somatostatin long-acting analogue
• Total bilirubin ≥ 60 µmol/L
• Uncontrolled diabetes
• Contraindication to product used in the study or its components
• Tumour arising in the context of a genetic disease
• Pregnancy or lactation
• Patients unable to undergo medical follow-up due to geographical, social, psychological or legal reasons
• Concomitant participation in another clinical trial investigating a treatment during the treatment phase and within 30 days prior to the start of the study treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lanreotide; In this arm, patients will receive lanreotide 120 mg every 28 days until disease progression	Drug: lanreotide; Patients will receive lanreotide 120 mg every 28 days until disease progression
Placebo Comparator: placebo; In this arm, patients will receive placebo every 28 days until disease progression	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Alive and Progression-free at 6 Months	The primary endpoint for this phase II study was the proportion of pts alive and progression-free at 6 months after randomisation, evaluated according to the results of the imaging assessment done by the investigator in line with RECIST 1.1 criteria.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	The progression-free survival is the time from inclusion to the first radiological progression or death (all causes). For patients alive without progression date of last news will be considered. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed durin the study (NADIR), or a measurable increase in a nontarget lesion, or the appearance of new lesions	up to 2 years
Overall Survival	Overall survival considered all deaths, and time was calculated from randomisation to death.	2 years after the end of the treatment

Collaborators and Investigators

• Sponsor: Federation Francophone de Cancerologie Digestive
• Investigators: Principal Investigator: Come Lepage, Pr, Federation Francophone de Cancerologie Digestive

Publications and helpful links

General Publications

• Lepage C, Dahan L, Bouarioua N, Toumpanakis C, Legoux JL, Le Malicot K, Guimbaud R, Smith D, Tougeron D, Lievre A, Cadiot G, Di Fiore F, Bouhier-Leporrier K, Hentic O, Faroux R, Pavel M, Borbath I, Valle JW, Rinke A, Scoazec JY, Ducreux M, Walter T. Evaluating lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours. Dig Liver Dis. 2017 May;49(5):568-571. doi: 10.1016/j.dld.2017.02.004. Epub 2017 Mar 11.
• Guiney DG Jr, Hasegawa P, Davis CE. Homology between clindamycin resistance plasmids in Bacteroides. Plasmid. 1984 May;11(3):268-71. doi: 10.1016/0147-619x(84)90035-0.
• Lepage C, Phelip JM, Lievre A, Le-Malicot K, Dahan L, Tougeron D, Toumpanakis C, Di-Fiore F, Lombard-Bohas C, Borbath I, Coriat R, Lecomte T, Guimbaud R, Petorin C, Legoux JL, Michel P, Scoazec JY, Smith D, Walter T. Lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours: An international double-blind, placebo-controlled randomised phase II trial - Prodige 31 REMINET: An FFCD study. Eur J Cancer. 2022 Nov;175:31-40. doi: 10.1016/j.ejca.2022.07.033. Epub 2022 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Maintenance treatment; Lanreotide; Duodeno-pancreatic neuroendocrine tumours
• 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; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Adenoma; Pancreatic Neoplasms; Neuroendocrine Tumors; Adenoma, Islet Cell; Antineoplastic Agents; Lanreotide
• Other Study ID Numbers: PRODIGE31