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

Study Overview
=================
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.

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

Conditions
-----------------
Metastatic/Locally Advanced, Non-resectable, Duodeno-pancreatic Neuroendocrine Tumours

Intervention / Treatment
-----------------
* Drug: lanreotide
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lanreotide, Duodeno-pancreatic neuroendocrine tumours, Maintenance treatment