Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine TumoursPhase 2/3REMINETNCT02288377

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

A Phase 2/3 study testing lanreotide in people with Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours, run by Federation Francophone de Cancerologie Digestive at 24 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours
What is being tested?: lanreotide
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 53 participants
Where: 24 sitesin 4 countries
Study dates: Jan 2015to Jan 2020
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 11Show fewer

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.

Who cannot join

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

Show all 11Show fewer

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.

Trial locations and contacts

24 sites in 4 countries.

Country

City, postcode or hospital

24 sites in 4 countries

France19 sites

CHU d'Angers - Hôtel Dieu
Angers
CHU - Hôpital Avicenne
Bobigny
CHU Côte de Nacre
Caen
CHU Estaing
Clermont-Ferrand
Hôpital Beaujon
Clichy
CHU Le Bocage Service d'HGE
Dijon, 21079
CH Les Oudairies
La Roche-sur-Yon
Hôpital Edouard Herriot
Lyon
CHU La Timone
Marseille
Hôpital de la Source
Orléans
CHU Cochin
Paris
Hôpital Haut Lévêque Bat Magellan, Service d'hépato-gastroentérologie
Pessac
Hôpital de la Milétrie
Poitiers
Hôpital Robert Debré
Reims
CHU de Rennes - Hôpital Pontchaillou
Rennes
CHU Charles Nicolle
Rouen
CHU de Saint Etienne
Saint-Priest-en-Jarez
Hôpital Rangueil
Toulouse
Institut Gustave Roussy
Villejuif

Other trials in France

Germany2 sites

Charite Campus Virchow Kilikum
Berlin
University Hospital Marburg
Marburg

Other trials in Germany

United Kingdom2 sites

Royal Free Hospital Neuroendocrine Tumour Unit
London
Manchester Academic Health Sciences Centre (MAHSC)
Manchester

Other trials in United Kingdom

Belgium1 site

Clinique Universitaire saint-Luc
Brussels

Other trials in Belgium

About this study

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

Read the 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.

Conditions: Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours
Being tested: lanreotide, Placebo
Keywords: Lanreotide, Duodeno-pancreatic neuroendocrine tumours, Maintenance treatment
Medical subject headings: Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

lanreotideDrug
Patients will receive lanreotide 120 mg every 28 days until disease progression
PlaceboDrug

Study groups in NCT02288377
Study group	Role	What they receive
lanreotide	Experimental	In this arm, patients will receive lanreotide 120 mg every 28 days until disease progression Receives: Drug: lanreotide
placebo	Placebo comparator	In this arm, patients will receive placebo every 28 days until disease progression Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 6 months

Secondary outcomes (2)

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
Measured: up to 2 years
Overall Survival
Overall survival considered all deaths, and time was calculated from randomisation to death.
Measured: 2 years after the end of the treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2015Jan 2020

First posted11 Nov 2014 (estimated)
Study startJan 2015
Primary completionJan 2020
Study completionJan 2020

Why it stopped: Because of slow recruitment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine TumoursStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02288377
Sponsor's protocol ID: PRODIGE31
Acronym: REMINET
Status last verified: Dec 2022
First submitted: 23 Sep 2014
Last updated: 18 Jan 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 28292641
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.
PubMed 6087395
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.
PubMed 36087395

Study at a glance

From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02288377
Acronym / sponsor ID: REMINET / PRODIGE31
Conditions: Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours
Keywords: Lanreotide, Duodeno-pancreatic neuroendocrine tumours, Maintenance treatment
Phase: Phase 2/3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Because of slow recruitment
Enrolment: 53 participants (actual)
Lead sponsor: Federation Francophone de Cancerologie DigestiveUniversity, hospital or other
Study start: Jan 2015 (actual)
Primary completion: Jan 2020 (actual)
Study completion: Jan 2020 (actual)
First posted: 11 Nov 2014 (estimated)
Results: Posted 4 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

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:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
lanreotide	Experimental	Drug: lanreotideIn this arm, patients will receive lanreotide 120 mg every 28 days until disease progression
placebo	Placebo comparator	Drug: PlaceboIn this arm, patients will receive placebo every 28 days until disease progression

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
lanreotidePatients will receive lanreotide 120 mg every 28 days until disease progression	Drug	lanreotide
Placebo	Drug	placebo

Primary outcome

Proportion of Patients Alive and Progression-free at 6 Months
Time frame: 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.

2 secondary outcomes

Progression-Free Survival
Time frame: up to 2 years
Overall Survival
Time frame: 2 years after the end of the treatment

Results and safety

Results posted to the registry on 4 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	26	25
Lanreotide	27	27

Primary outcome: Proportion of Patients Alive and Progression-free at 6 Months

Time frame: 6 months. Count of participants. Unit: Participants

Measure	Placebo n = 24	Lanreotide n = 26
Value	13	19

Population analysed: 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to the end of treatment, on average of 24 months. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	3 of 25 (12%)	6 of 25 (24%)	7 of 25
Lanreotide	5 of 27 (18.5%)	9 of 27 (33.3%)	2 of 27

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28292641Lepage 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.
Results publication: PubMed 6087395Guiney 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.
Derived from this study: PubMed 36087395Lepage 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Come Lepage, Pr principal investigator

Federation Francophone de Cancerologie Digestive

24 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in France, Germany, United Kingdom, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients Alive and Progression-free at 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02288377, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.