Clinical trial NCT02288377: A Study Evaluating Lanreotide as Maintenance Therapy in Patients With Non-Resectable Duodeno-Pancreatic Neuroendocrine Tumors (REMINET)
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours
Keywords: Lanreotide
Duodeno-pancreatic neuroendocrine tumours
Maintenance treatment
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2014-11-11
Enrollment: 53
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 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.

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.

Eligibility 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%)
* 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.

Primary outcomes:
measure: Proportion of Patients Alive and Progression-free at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: 2 years after the end of the treatment
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Clinique Universitaire saint-Luc
city: Angers
country: France
facility: CHU d'Angers - Hôtel Dieu
city: Bobigny
country: France
facility: CHU - Hôpital Avicenne
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Clichy
country: France
facility: Hôpital Beaujon
city: Dijon Cedex
country: France
facility: CHU Le Bocage Service d'HGE
city: La Roche Sur Yon
country: France
facility: CH Les Oudairies
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: CHU La Timone
city: Orléans
country: France
facility: Hôpital de la Source
city: Paris
country: France
facility: CHU Cochin
city: Pessac
country: France
facility: Hôpital Haut Lévêque Bat Magellan, Service d'hépato-gastroentérologie
city: Poitiers
country: France
facility: Hôpital de la Milétrie
city: Reims
country: France
facility: Hôpital Robert Debré
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Saint Priest En Jarez
country: France
facility: CHU de Saint Etienne
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Campus Virchow Kilikum
city: Marburg
country: Germany
facility: University Hospital Marburg
city: London
country: United Kingdom
facility: Royal Free Hospital Neuroendocrine Tumour Unit
city: Manchester
country: United Kingdom
facility: Manchester Academic Health Sciences Centre (MAHSC)
Study officials:
affiliation: Federation Francophone de Cancerologie Digestive
name: Come Lepage, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.