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Neuroendocrine TumorsEarly Phase 1MetNET-2NCT02823691

The MetNET-2 Trial

A Early Phase 1 study testing Lanreotide and Metformin in people with Neuroendocrine Tumors, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors
What is being tested?
Lanreotide and Metformin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteItaly
Study dates
Apr 2016to Dec 2021
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • 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
Show all 22Show fewer
  • 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.

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • NationalCIMilan

    Milan, 20133

Other trials in Italy

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
Lanreotide and Metformin
Keywords
NETs
Medical subject headings
Neuroendocrine Tumors

What participants receive

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

  • Lanreotide and MetforminDrug

    Also called Ipstyl and Metformin

    Lanreotide and Metformin

Study groups in NCT02823691
Study groupRoleWhat they receive
Lanreotide and MetforminExperimentalDose 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.
Receives: Drug: Lanreotide and Metformin

What is being measured

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

  1. incidence of SAEs and AEs

    Measured: 1 year

Secondary outcomes (3)

  1. 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

    Measured: 3 years

  2. 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).

    Measured: 1 year

  3. 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

    Measured: 1 year

Timeline

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

  1. First posted6 Jul 2016 (estimated)
  2. Study startApr 2016
  3. Primary completionDec 2021 (estimated)
  4. Study completionDec 2021 (estimated)

Resources

More details

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

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02823691
Sponsor's protocol ID
NationalCIMilan
Acronym
MetNET-2
Status last verified
Jun 2021
First submitted
19 May 2016
Last updated
7 Jun 2021
Results posted
No
Data monitoring committee
No

Publications

  • Culler MD, Oberg K, Arnold R, Krenning EP, Sevilla I, Diaz JA. Somatostatin analogs for the treatment of neuroendocrine tumors. Cancer Metastasis Rev. 2011 Mar;30 Suppl 1:9-17. doi: 10.1007/s10555-011-9293-0.

    PubMed 21369878

  • Rizos CV, Elisaf MS. Metformin and cancer. Eur J Pharmacol. 2013 Apr 5;705(1-3):96-108. doi: 10.1016/j.ejphar.2013.02.038. Epub 2013 Mar 13.

    PubMed 23499688

  • Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlackova E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33. doi: 10.1056/NEJMoa1316158.

    PubMed 25014687

  • Vlotides G et Al: anticancer effects of metformin on neuroendocrine tumor cell in vitro. 10 the ENETs Annual conference Barcelona 5-8 March 2013

  • Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005 Jun 4;330(7503):1304-5. doi: 10.1136/bmj.38415.708634.F7. Epub 2005 Apr 22. No abstract available.

    PubMed 15849206

  • Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, Gandini S. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010 Nov;3(11):1451-61. doi: 10.1158/1940-6207.CAPR-10-0157. Epub 2010 Oct 12.

    PubMed 20947488

  • Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009 Jul 10;27(20):3297-302. doi: 10.1200/JCO.2009.19.6410. Epub 2009 Jun 1.

    PubMed 19487376

  • Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41. doi: 10.1161/01.RES.0000256090.42690.05.

    PubMed 17307971

  • Vazquez-Martin A, Oliveras-Ferraros C, del Barco S, Martin-Castillo B, Menendez JA. mTOR inhibitors and the anti-diabetic biguanide metformin: new insights into the molecular management of breast cancer resistance to the HER2 tyrosine kinase inhibitor lapatinib (Tykerb). Clin Transl Oncol. 2009 Jul;11(7):455-9. doi: 10.1007/s12094-009-0384-0.

    PubMed 19574203

  • Vazquez-Martin A, Oliveras-Ferraros C, Lopez-Bonet E, Menendez JA. AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor. Cell Cycle. 2009 Nov 15;8(22):3679-83. doi: 10.4161/cc.8.22.9905. Epub 2009 Nov 24.

    PubMed 19844168

  • O'Toole D, Ducreux M, Bommelaer G, Wemeau JL, Bouche O, Catus F, Blumberg J, Ruszniewski P. Treatment of carcinoid syndrome: a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer. 2000 Feb 15;88(4):770-6. doi: 10.1002/(sici)1097-0142(20000215)88:43.0.co;2-0.

    PubMed 10679645

  • CLARINET Abstract E17-7103, Amsterdam EJC, vol 49 (3), 2013

  • Martin-Richard M, Massuti B, Pineda E, Alonso V, Marmol M, Castellano D, Fonseca E, Galan A, Llanos M, Sala MA, Pericay C, Rivera F, Sastre J, Segura A, Quindos M, Maisonobe P; TTD (Tumores del Tracto Digestivo) Study Group. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study. BMC Cancer. 2013 Sep 20;13:427. doi: 10.1186/1471-2407-13-427.

    PubMed 24053191

  • Machin, D., Campbell, M., Fayers, P., and Pinol, A. 1997. Sample Size Tables for Clinical Studies, 2nd edition. Blackwell Science. Malden, MA.

  • Cohen J. (1988) Statistical Power Analysis fo the Behavioural Sciences, Lawrence Erbaum Associates, Hillsdale, New Jersey.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Lanreotide and Metformin in people with Neuroendocrine Tumors, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

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 22 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 7 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this study?

Results are not available in the source record.

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?

incidence of SAEs and AEs (time frame: 1 year). 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 NCT02823691, which also lists 38 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 7 Jun 2021.

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