The MetNET-2 Trial

Study Overview
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Brief Summary
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This is a Pilot, One-arm, Open-label, Prospective Study to evaluate Safety of Lanreotide 120 mg ATG in combination with Metformin in patients with advanced progressive GI or lung carcinoids. The patient population will include patients with a histologically documented diagnosis of Well differentiated NET, G1-G2 according to the last WHO Classification criteria for GI and lung NET carcinoids.

Detailed Description
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This study is strategically positioned in the medical treatment safety and efficacy context, that is Lanreotide can be safely and effectively used in combination with other agents, like Metformin. Aim of this study is to verify the safety of a concomitant administration of Lanreotide 120 mg ATG with Metformin in advanced, progressing gastro-intestinal or lung carcinoids patients, by accurately monitor patients from a tolerability point of view during all study long.

Official Title
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Safety of Lanreotide 120 mg ATG in Combination With Metformin in Patients With Progressive Advanced Well-differentiated Gastro-intestinal (GI) or Lung Carcinoids: A Pilot, One-arm, Open-label, Prospective Study: the MetNET-2 Trial

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Lanreotide and Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (male or female, age > 18 years) Patient with advanced disease, not resectable. The evaluation of unresectable disease will be performed by surgeon of multidisciplinary Milan ENETS Center of Excellence tumour board of Fondazione IRCCS Istituto Nazionale dei Tumori Milano. Patients with a histologically documented diagnosis of advanced well differentiated (G1 and G2) GI or lung carcinoids, defined according to the last WHO Classification criteria for NET Tumor tissue available for analysis Measurable disease and disease progression in the 6 months before study inclusion (according to RECIST vs 1.1), documented and appropriate imaging Patient who has received prior treatment with surgery or chemotherapy or somatostatin analogues or m-TOR inhibitors or other systemic antineoplastic/target therapies Functioning or non-functioning NETs Type-2 Diabetic or normoglycaemic patient Documented Octreoscan/PET Ga68 uptake/IHC stain of SSTR2 receptor, within 6 months before study entry Basal blood tests: Counts of neutrophils in absolute value> 1.5 x 103 / L Platelet count> 100 x 103 / L Hemoglobin> 9 g/dl Total Bilirubin <1.5 times the upper limit of normal AST, ALT <2.5 times the upper limit of normal Alkaline phosphatase <2.5 times the upper limit of normal Values of serum creatinine <1.5 mg / dl. - CCr ≥ 60 mL / min ECOG performance status ≤ 2 Life expectancy > 12 months Written informed consent Female subjects of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for at least 60 days after participation in the study. Acceptable methods of contraception include double barrier method [i.e. condom and occlusive cap (diaphragm or cervical/vault caps)] spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. Male subjects with female partners of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 60 days after participation in the study. Exclusion Criteria Surgery performed within 28 days prior to the beginning of study treatment Brain metastasis or spinal cord compression Type-1 Diabetes Clinically significant cardiovascular disease, such as cardiovascular accidents occurred in less than 6 months, unstable angina, congestive heart failure grade greater than or equal to II (according to the classification of the New York Heart Association NYHA) series cardiac arrhythmias that require treatment Uncontrolled high blood pressure, atrial fibrillation Cardio-vascular, lung, kidney or hepatic disorders not treated/controlled Cirrhosis, acute hepatitis or chronic active hepatitis Metabolic disorders, clinical examination or laboratory investigations which contraindicate the use of drugs to study, or patients at high risk of complications from the treatment Active or uncontrolled severe infections Patients with a condition of metabolic acidosis, acute or chronic, including ketoacitosi History of POTUS (alcohol abuse), or habitual intake of alcohol (≥ 3 glasses of alcoholic drinks / day) sufficient to cause hepatotoxicity Severe states of dehydration Prolonged fasting History of immunosuppression, including positive HIV test Previous or concomitant oncological pathology, except: basal cell skin cancer, in situ, as long as every other cancer patient disease-free for at least 5 years Serious neurological or psychiatric disorders Pregnancy or lactation Patients that do not use appropriate methods of contraception as specified in the inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lanreotide and Metformin<br>Dose and Treatment Regimen: LANREOTIDE ATG 120 mg/28 days (equivalent to 1 cycle), deep subcutaneous injection (SC) in combination with METFORMIN 2550 mg daily (maximum dose), oral administration (OS). Metformin starting dose 850 mg/day to be increased up to 1700 mg/day at day 14, 2550 mg/day at day 28, (maximum dose), if well tolerated. | Drug: Lanreotide and Metformin<br>* Lanreotide and Metformin<br>* Other names: Ipstyl and Metformin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of SAEs and AEs |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression (TTP) to Lanreotide ATG 120 mg in combination with Metformin | This is a pilot study. This endpoints should be considered an exploratory evaluation | 3 years | 
| symptomatic responses to Lanreotide ATG 120 mg in combination with Metformin in symptomatic patients | Answers will be based on a 5 point Likert scale (1=completely satisfied, 2= rather satisfied, 3= unchanged, 4= rather dissatisfied, 5= completely dissatisfied). | 1 year | 
| biochemical responses to Lanreotide ATG 120 mg in combination with Metformin | Biochemical progression will be evaluated testing Chromogranin A, NSE, 5-HIAA (only if functioning tumours) at each 4th month | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NETs