Clinical trial realized in several centers and in several European countries to evaluate a maintenance treatment by lanreotide in patients having neuroendocrine tumors, localized in duodenum or pancreas. Lanreotide will be compared with the placebo, and neither the patients nor the doctors will know the treatment taken by the patients

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2013-004069-14-BE
• Date of registration: 09/09/2014
• Prospective Registration: Yes
• Primary sponsor: Fédération Francophone de Cancérologie Digestive (FFCD)
• Public title: Clinical trial realized in several centers and in several European countries to evaluate a maintenance treatment by lanreotide in patients having neuroendocrine tumors, localized in duodenum or pancreas. Lanreotide will be compared with the placebo, and neither the patients nor the doctors will know the treatment taken by the patients
• Scientific title: 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 - REMINET
• Date of first enrolment: 17/11/2014
• Target sample size: 222
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004069-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Germany, Ireland, United Kingdom

Contacts

• Name: Pascale Brosset-Savigny
• Affiliation: ICTA PM

• Name: Pascale Brosset-Savigny
• Affiliation: ICTA PM

Key inclusion & exclusion criteria

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%)
•First-line treatment started due to (a, b OR c):
a. Presence of symptomatic disease and/or hepatic invasion = 50%
and/or bone metastasis
b. Documented tumour progression before first line treatment
c. Disease progression under Somatostatin analogues (analogues
stopped prior to starting the 1st 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 targeted therapy (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 targeted therapy
•Non-functional tumour or gastrinoma controlled by PPIs
•Age > or = 18 years
•WHO 0, 1 or 2
•Highly effective contraception for male or female patients of
childbearing age, defined as: oral contraceptives, intra-uterine devices
or surgical sterilisation (vasectomy, tubal ligation). 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 111
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 111

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
•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.
•Employment of the subject or a close relative (i.e. spouse/partner,
child, parent or sibling) by the CRO, the study site
•Patients deprived of their liberty by a judicial or administrative
decision, patients admitted to a hospital, social institution or who are
under a measure of legal protection, patients hospitalized without
consent or who are in an emergency situation.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-resectable duodeno-pancreatic neuroendocrine tumours after first line treatment
MedDRA version: 19.0 Level: PT Classification code 10067517 Term: Pancreatic neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: SOMATULINE® LP 120 mg
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: LANREOTIDE
CAS Number: 108736-35-2
Current Sponsor code: BN 52030, BIM-23014C
Other descriptive name: Lanreotide acetate [127984-74-1]
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: Phase II:
•Rate of patients alive and progression free at 12 months, assessed by the investigator according to RECIST criteria (version 1.1)
•Rate of patients alive and progression free at 6 months, according to central review
•Safety
•Response rate at 6 months according to RECIST criteria (version 1.1)
•Time To Progression (TTP)
•Quality of life assessed with the questionnaire QLQ-C30, including module NET 21, and the Spitzer visual analogue scale.

Phase III:
•Overall Survival (OS) at 3 and 5 years
•PFS according to central review
•Safety
•Response rate at 6 months according to RECIST criteria (version 1.1)
•Chemotherapy / biotherapy-free time interval
•Quality of life assessed with the questionnaire QLQ-C30, including module NET 21, and the Spitzer visual analogue scale.
•Medico-economical evaluation: cost-effectiveness analysis at 12 months and cost-utility analysis at 18 months (using EQ-5D questionnaire).

Primary end point(s): Phase II:
The rate of patients alive and progression free at 6 months, evaluated according to the results of imaging assessment done 6 months after the randomisation. This evaluation will be done by the investigator according to RECIST criteria (version 1.1).

Phase III:
The progression free survival, considering the first radiological progression of the patient (investigator’s opinion) or death (any reason). The time will be calculated between the randomisation date and the date the first event occurred. Patients who are alive and progression free will be censored at the time of the last news or cut-off date (the date the first of these occurs will be considered).

Timepoint(s) of evaluation of this end point: Phase II:
At 6 months

Phase III:
Approximately 10 years

Main Objective: Phase II:
To evaluate the rate of patients alive and progression free at 6 months, assessed by the investigator according to RECIST criteria, version 1.1.

Phase III:
To assess and compare the Progression Free Survival (PFS) of lanreotide versus placebo according to RECIST criteria (version 1.1, Appendix 3), assessed by the investigator.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Phase II:
At 6 months, 12 months and first progression (clinical and radiological) according to the investigator

Phase III:
At 6 months, 12 months, 18 months, 3 years, 5 years, and first radiological progression of the patient (central review) or death (whatever the reason).

Secondary end point(s): Phase II:
•Rate of patients alive and progression free at 12 months (according to RECIST criteria version 1.1), assessed by the investigator
•Rate of patients alive and progression free at 6 months, according to central review
•Safety: the toxicities will be described using the NCI-CTC AE version 4.0
•Response rate according to RECIST criteria at 6 months (version 1.1), according to the investigator. Response rate will be defined as complete or partial response to the treatment
•Time to progression (median). This endpoint will be calculated from the randomisation date to the date of the first progression (clinical and radiological) according to the investigator
•Quality of life (QLQ-C30 including module NET 21, the Spitzer visual analogue scale) will be described at each time-point.

Phase III:
The secondary endpoints of phase III will consist of the comparison between the placebo and the lanreotide, on:
•Overall survival (OS) at 3 and 5 years. This endpoint will be estimated considering all deaths and the time will be calculated from the randomisation date to the date of death. Patients alive will be censored at the date of the last news or at the cut-off date
•PFS according to central review, evaluated considering the first radiological progression of the patient (central review) or death (any reason). The time will be calculated from the randomisation date to the date the first event occurred. Patients alive and progression free will be censored at the date of the last news or at the cut-off date (the date the first of these occurs will be considered).
•Safety: the toxicities will be described using the NCI-CTC AE version 4.0
•Response rate at 6 months according to RECIST criteria (version 1.1). Response rate will be defined as complete or partial response to the treatment
•Chemotherapy/targeted therapy-free time interval: the time will be calculated from the last chemotherapy/ targeted therapy (first-line treatment) administration, to the date of restart of first-line treatment or to the start of a new line (second-line treatment).
•Quality of life (QLQ-C30 including module NET 21, the Spitzer visual analogue scale) will be described at each time-point
•Average cost at 12 and 18 months
•Effectiveness average at 12 and 18 months and utility index score average at 18 months using EQ-5D questionnaire.
•Efficiency:
- At 12 months; cost per progression free life year gained (PFLYG)
- At 18 months: cost per PFLYG and cost per PFLYG adjusted for quality of life (QAPFLYG).

Secondary ID(s)

2013-004069-14-DE

PRODIGE31

Source(s) of Monetary Support

IPSEN

Ethics review

Status: Approved
Approval date: 17/11/2014
Contact: