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

• Sponsor: Federation Francophone de Cancerologie Digestive (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02288377
• Collaborator: (none)
• Enrollment: 53
• Locations: 24
• Arms: 2
• Actual Duration (Months): 60
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours	Drug: lanreotide; Drug: Placebo	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jan 1, 2020
• Actual Study Completion Date: Jan 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Alive and Progression-free at 6 Months [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.

Secondary Outcome Measures

1. Progression-Free Survival [up to 2 years]

   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

2. Overall Survival [2 years after the end of the treatment]

   Overall survival considered all deaths, and time was calculated from randomisation to death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinique Universitaire saint-Luc	Bruxelles		Belgium
2	CHU d'Angers - Hôtel Dieu	Angers		France
3	CHU - Hôpital Avicenne	Bobigny		France
4	CHU Côte de Nacre	Caen		France
5	CHU Estaing	Clermont Ferrand		France
6	Hôpital Beaujon	Clichy		France
7	CHU Le Bocage Service d'HGE	Dijon Cedex		France	21079
8	CH Les Oudairies	La Roche Sur Yon		France
9	Hôpital Edouard Herriot	Lyon		France
10	CHU La Timone	Marseille		France
11	Hôpital de la Source	Orléans		France
12	CHU Cochin	Paris		France
13	Hôpital Haut Lévêque Bat Magellan, Service d'hépato-gastroentérologie	Pessac		France
14	Hôpital de la Milétrie	Poitiers		France
15	Hôpital Robert Debré	Reims		France
16	CHU de Rennes - Hôpital Pontchaillou	Rennes		France
17	CHU Charles Nicolle	Rouen		France
18	CHU de Saint Etienne	Saint Priest En Jarez		France
19	Hôpital Rangueil	Toulouse		France
20	Institut Gustave Roussy	Villejuif		France
21	Charite Campus Virchow Kilikum	Berlin		Germany
22	University Hospital Marburg	Marburg		Germany
23	Royal Free Hospital Neuroendocrine Tumour Unit	London		United Kingdom
24	Manchester Academic Health Sciences Centre (MAHSC)	Manchester		United Kingdom

Sponsors and Collaborators

• Federation Francophone de Cancerologie Digestive

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Nov 3, 2014
• Statistical Analysis Plan - Dec 3, 2019

More Information

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.

• Responsible Party: Federation Francophone de Cancerologie Digestive
• ClinicalTrials.gov Identifier: NCT02288377
• Other Study ID Numbers: PRODIGE31
• First Posted: Nov 11, 2014
• Last Update Posted: Oct 4, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Federation Francophone de Cancerologie Digestive: Lanreotide; Duodeno-pancreatic neuroendocrine tumours; Maintenance treatment
• Additional relevant MeSH terms: Neuroendocrine Tumors; Adenoma, Islet Cell; Lanreotide

Study Results

Participant Flow

Recruitment Details	Fifty-three pts were randomised in 15 centres between January 2015 and October 2018.
Pre-assignment Detail	The study was terminated prematurely because of slow recruitment.

Arm/Group Title	Placebo	Lanreotide
Arm/Group Description	Patients will receive placebo every 28 days until disease progression	Patients will receive lanreotide 120 mg every 28 days until disease progression
Period Title: Overall Study
STARTED	26	27
COMPLETED	25	27
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Placebo	Lanreotide	Total
Arm/Group Description	Patients will receive placebo every 28 days until disease progression	Patients will receive lanreotide 120 mg every 28 days until disease progression	Total of all reporting groups
Overall Participants	26	27	53
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (12.45)	65.22 (10.30)	63.25 (11.47)
Sex: Female, Male (Count of Participants)
Female	13 50%	12 44.4%	25 47.2%
Male	13 50%	15 55.6%	28 52.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Belgium	0 0%	1 3.7%	1 1.9%
United Kingdom	1 3.8%	1 3.7%	2 3.8%
France	25 96.2%	25 92.6%	50 94.3%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Alive and Progression-free at 6 Months
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Lanreotide
Arm/Group Description	Patients will receive placebo every 28 days until disease progression	Patients will receive lanreotide 120 mg every 28 days until disease progression
Measure Participants	24	26
Count of Participants [Participants]	13 50%	19 70.4%

2. Secondary Outcome

Title	Progression-Free Survival
Description	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
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

Outcomes was evaluated on patients randomized and receiving at least one dose of treatment

Arm/Group Title	Placebo	Lanreotide
Arm/Group Description	Patients will receive placebo every 28 days until disease progression	Patients will receive lanreotide 120 mg every 28 days until disease progression
Measure Participants	25	27
Median (95% Confidence Interval) [Months]	7.6	19.4

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival considered all deaths, and time was calculated from randomisation to death.
Time Frame	2 years after the end of the treatment

Outcome Measure Data

Analysis Population Description

The outcome was evaluated on randomized patients who received at least one dose of treatment

Arm/Group Title	Placebo	Lanreotide
Arm/Group Description	Patients will receive placebo every 28 days until disease progression	Patients will receive lanreotide 120 mg every 28 days until disease progression
Measure Participants	25	27
Number (95% Confidence Interval) [Percentage of patients alive]	86.1	95.0

Adverse Events

Time Frame	Up to the end of treatment, on average of 24 months
Adverse Event Reporting Description	Toxicities were collected before each injection of treatment up to the end of the treatment each 28 days. The study treatment was given until withdrawal of the patients for any reason (Toxicities, progression or any other medical reason)
Arm/Group Title	Placebo		Lanreotide
Arm/Group Description	Patients will receive placebo every 28 days until disease progression		Patients will receive lanreotide 120 mg every 28 days until disease progression
All Cause Mortality
	Placebo		Lanreotide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/25 (28%)		2/27 (7.4%)
Serious Adverse Events
	Placebo		Lanreotide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/25 (12%)		5/27 (18.5%)
Gastrointestinal disorders
Constipation	1/25 (4%)		0/27 (0%)
Small intestinal obstruction	1/25 (4%)		0/27 (0%)
Peritoneal haemorrhage	0/25 (0%)		1/27 (3.7%)
Gastrointestinal haemorrhage	0/25 (0%)		1/27 (3.7%)
Abdominal pain upper	0/25 (0%)		1/27 (3.7%)
General disorders
Pyrexia	0/25 (0%)		1/27 (3.7%)
Hepatobiliary disorders
Cholangitis and Malignant biliary obstruction	0/25 (0%)		1/27 (3.7%)
Cholangitis and Cholecystitis acute	0/25 (0%)		1/27 (3.7%)
Metabolism and nutrition disorders
Hypokalaemia	1/25 (4%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Lanreotide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/25 (24%)		9/27 (33.3%)
Gastrointestinal disorders
Abdominal Pain	1/25 (4%)		1/27 (3.7%)
Gastrointestinal haemorrhage	1/25 (4%)		1/27 (3.7%)
Diarrhoea	0/25 (0%)		2/27 (7.4%)
Vomiting	1/25 (4%)		1/27 (3.7%)
General disorders
Asthenia	1/25 (4%)		2/27 (7.4%)
Hepatobiliary disorders
Cholangitis	1/25 (4%)		0/27 (0%)
Cholecystitis acute	1/25 (4%)		0/27 (0%)
Malignant biliary obstruction	1/25 (4%)		0/27 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	0/25 (0%)		1/27 (3.7%)
Hyperglycaemia	0/25 (0%)		1/27 (3.7%)
Hypoglycaemia	0/25 (0%)		1/27 (3.7%)
Hypokalaemia	0/25 (0%)		1/27 (3.7%)
Hypophosphataemia	0/25 (0%)		1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.