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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Apr 2016 → ongoing

Decision date (initial)

2024-06-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513200-34-00

EudraCT number

2015-004626-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the safety of Lanreotide ATG 120 mg in combination with Metformin as number of AEs and SAEs.

Secondary objectives 3

1. To evaluate the time to progression (TTP) to Lanreotide ATG 120 mg in combination with Metformin
2. To evaluate the symptomatic responses to Lanreotide ATG 120 mg in combination with Metformin in symptomatic patients
3. To evaluate the biochemical responses to Lanreotide ATG 120 mg in combination with Metformin

Conditions and MedDRA coding

advanced progressive gastro-intestinal or lung carcinoids

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Adult patients (male or female, age > 18 years)
2. 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.
3. 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
4. Tumor tissue available for analysis
5. Measurable disease and disease progression in the 6 months before study inclusion (according to RECIST vs 1.1), documented and appropriate imaging
6. Patient who has received prior treatment with surgery or chemotherapy or somatostatin analogues or m-TOR inhibitors or other systemic antineoplastic/target therapies
7. Functioning or non-functioning NETs
8. Type-2 Diabetic or normoglycaemic patient
9. Documented Octreoscan/PET Ga uptake/IHC stain of SSTR2 receptor, within 6 months before study entry
10. 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
11. ECOG performance status ≤ 2
12. Life expectancy > 12 months
13. Written informed consent
14. 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.
15. 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 18

1. Surgery performed within 28 days prior to the beginning of study treatment
2. Brain metastasis or spinal cord compression
3. Type-1 Diabetes
4. 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
5. Uncontrolled high blood pressure, atrial fibrillation
6. Cardio-vascular, lung, kidney or hepatic disorders not treated/controlled
7. Cirrhosis, acute hepatitis or chronic active hepatitis
8. 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
9. Active or uncontrolled severe infections
10. Patients with a condition of metabolic acidosis, acute or chronic, including ketoacitosi
11. History of POTUS (alcohol abuse), or habitual intake of alcohol (≥ 3 glasses of alcoholic drinks / day) sufficient to cause hepatotoxicity
12. Severe states of dehydration
13. Prolonged fasting
14. History of immunosuppression, including positive HIV test
15. 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
16. Serious neurological or psychiatric disorders
17. Pregnancy or lactation
18. Patients that do not use appropriate methods of contraception as specified in the inclusion criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the incidence of SAEs and AEs, physical examination output, laboratory tests results, and cardiologic assessment, during treatment study period.

Secondary endpoints 2

1. To evaluate the efficacy of Lanreotide ATG 120 mg in combination with Metformin on the time to progression (TTP), defined as the time from first study drugs administration (Lanreotide 120 mg plus Metformin) to the first radiological or clinical or biochemical progression or tumor-related death, according to RECIST criteria vs 1.1.
2. To evaluate the efficacy of Lanreotide ATG 120 mg in combination with Metformin on symptomatic response.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical Trials Center

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical Trials Center

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications