Assessment of Retreatment With Lutathera® in Patients With New Progression of Intestinal Well-differenciated NET

NCT04954820 | Recruiting Phase 2

• 1 other identifier: PROICM 2021-04 REL
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 28

Brief Summary

In France, since the reimbursement of Lutathera®, this treatment is allowed for retreatment if patients still fulfill the criteria of its indication and 4 news cycles could be proposed. However, clinical practices are heterogeneous regarding the number of new cycles and most teams perform only two additional cycles (every 8 weeks). Therefore, the coordinator propose to evaluate the efficacy of two additional cycle of Lutathera® versus active surveillance in patients already retreated with two cycles Lutathera® for a new progression of intestinal neuroendocrine tumor and who previously received the 4 cycles of treatment with a clinical benefit.

Conditions

Neuroendocrine Tumors; Intestinal Well Differentiated Endocrine Tumor; Progressive Disease

Outcome Measures

Primary Outcomes (1)

• Evaluate the efficacy of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance during 6 months in patients already retreated with two cycles.

  defined as a change of tumoral assessment (Complete Response, Partial Response and Stable Disease from RECIST v1.1) with an evaluation every 2 months.

  assessement every cycle (every 8 weeks) 6 months from randomization

Secondary Outcomes (5)

• Evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance in term of Safety

  during 6 months in patients already retreated with two cycles (each cycle is 8 weeks)

• Evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance in term of Progression free survival

  the time without progression of disease during 5 years after the treatment,

• Evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance in term of Overall survival

  the time without death during 5 years after the treatment

• To assess quality of life of general patient

  during and after treatment in both arm : every 8 wweks during the treatment, every 3 months during 1 year post treatment and every year during 4 years post treatment

• To assess quality of life of gastrointestinal neuroendocrine tumor

  during and after treatment in both arm : every 8 wweks during the treatment, every 3 months during 1 year post treatment and every year during 4 years post treatment

Study Arms (2)

Experimental arm

EXPERIMENTAL

2 additional infusions of Lutathera® according to the marketing authorization schema

Drug: Lutathera

Control arm

NO INTERVENTION

No treatment with active monitoring (clinical, biological and radiological follow-up) every 2 months.

Interventions

Lutathera DRUG

2 additional infusions of Lutathera®

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years,
• Histologically proven intestinal G1 or G2 neuroendocrine tumors (NET),
• Patient previously treated with 4 cycles of Lutathera® (defined as "First PRRT"),
• Disease control after "First PRRT" ≥ 12 months,
• Patient presenting a progression of disease (clinic, biologic and/or radiologic) after a first PRRT,
• Decision of retreatment with Lutathera® (defined as "Second PRRT") validated by RENATEN and/or multidisciplinary tumor board and in the scope of the French reimbursement process,
• ECOG performance status 0-2,
• Life expectancy ≥ 6 months as prognosticated by the physician,
• Measurable disease per RECIST 1.1 (Appendix 1), on CT/MRI scans, defined as at least 1 lesion with ≥ 1 cm in longest diameter, and ≥ 2 radiological tumors lesions in total,
• Adequate bone marrow reserve (Hb \> 8 g/dl, neutrophils ≥ 1500/mm³ and platelets ≥ 80 000/mm³),
• Effective contraception in men or women of childbearing or pre-menopausal age and up to a minimum of 6 months following the end of treatment,
• Patient´s signed written informed consent,
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures,
• Affiliation to the French Social Security System

You may not qualify if:

• Patient who did not respond (no CR, PR or SD) to "first PRRT".
• Radiological progression after two cycles of "Second PRRT" according to RECIST version 1.1,
• Grade 4 hematotoxicity and/or nephrotoxicity during the initial PRRT, or unresolved AEs categorized as Grade 2 or higher (as per Common Terminology Criteria for Adverse Events (CTCAE v5.0) from previous PRRT cycles or any other therapy for NET, excluding alopecia and peripheral neuropathy,
• Pancreatic NET,
• NeuroEndocrine Carcinoma,
• Prior external beam radiation therapy to more than 25% of the bone marrow,
• Severe renal (estimated Glomerular Filtration Rate (GFR) according to Modification of Diet in Renal Disease (MDRD) \< 40 mL/min or nephrotic syndrome) or hepatic insufficiency (Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) \> 2.5 x ULN or ALT/AST \> 5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin \> 2.5 x ULN),
• Serum albumin \< 3.0 g/dL unless prothrombin time is within the normal range,
• Uncontrolled diabetes mellitus as defined by a fasting blood glucose above 2 ULN,
• Uncontrolled decompensated heart failure, myocardial infarction uncontrolled, stroke, pulmonary embolism or revascularization procedure, unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months,
• Hypertension that cannot be controlled despite medications (≥ 160/95 mmHg despite optimal medical therapy)
• Brain metastases (unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases must have a head CT scan with contrast or MRI to document stable disease prior to enrolment in the study),
• Pregnancy or breast feeding,
• Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results,
• Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products,

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (28)

Institut de Cancérologie de l'Ouest Site d'Angers

Angers, 49055, France

RECRUITING

Institut Bergonié

Bordeaux, 33000, France

RECRUITING

CHRU Morvan

Brest, 29200, France

RECRUITING

Hospices civils de LYON - GHE

Bron, 69677, France

RECRUITING

Centre François Baclesse

Caen, 14076, France

RECRUITING

CH Métropole de Savoie

Chambéry, 73011, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

Hopital Beaujon

Clichy, 92110, France

RECRUITING

CHU de DIJON

Dijon, 21079, France

RECRUITING

CHU Grenoble Alpes (CHUGA)

La Tronche, 38700, France

RECRUITING

CHRU Lille

Lille, 59000, France

RECRUITING

Centre léon bérard

Lyon, 69008, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

Hôpital de la Timone

Marseille, 13385, France

RECRUITING

ICM Val d'Aurelle

Montpellier, 34298, France

RECRUITING

CHU Nantes

Nantes, 44093, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Hôpital Pitié Salpétrière

Paris, 75013, France

RECRUITING

Hôpital Cochin

Paris, 75014, France

RECRUITING

Hôpital Haut-Lévêque

Pessac, 33604, France

RECRUITING

Centre Henri Becquerel

Rouen, 76000, France

RECRUITING

CHU de Rouen

Rouen, 76031, France

NOT YET RECRUITING

CHU ST Etienne

Saint-Etienne, 42055, France

RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44805, France

RECRUITING

Institut de cancérologie Strasbourg

Strasbourg, 67033, France

RECRUITING

IUCT Oncopole

Toulouse, 31100, France

RECRUITING

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Related Publications (12)

• Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20;26(18):3063-72. doi: 10.1200/JCO.2007.15.4377.

  PMID: 18565894 BACKGROUND

• Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Oberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.

  PMID: 28076709 BACKGROUND

• Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum RP, Kunz P, Hobday T, Hendifar A, Oberg K, Sierra ML, Thevenet T, Margalet I, Ruszniewski P, Krenning E; NETTER-1 Study Group. Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial. J Clin Oncol. 2018 Sep 1;36(25):2578-2584. doi: 10.1200/JCO.2018.78.5865. Epub 2018 Jun 7.

  PMID: 29878866 BACKGROUND

• Rudisile S, Gosewisch A, Wenter V, Unterrainer M, Boning G, Gildehaus FJ, Fendler WP, Auernhammer CJ, Spitzweg C, Bartenstein P, Todica A, Ilhan H. Salvage PRRT with 177Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival. BMC Cancer. 2019 Aug 8;19(1):788. doi: 10.1186/s12885-019-6000-y.

  PMID: 31395036 BACKGROUND

• Vaughan E, Machta J, Walker M, Toumpanakis C, Caplin M, Navalkissoor S. Retreatment with peptide receptor radionuclide therapy in patients with progressing neuroendocrine tumours: efficacy and prognostic factors for response. Br J Radiol. 2018 Nov;91(1091):20180041. doi: 10.1259/bjr.20180041. Epub 2018 Mar 20.

  PMID: 29513039 BACKGROUND

• Yordanova A, Mayer K, Brossart P, Gonzalez-Carmona MA, Strassburg CP, Essler M, Ahmadzadehfar H. Safety of multiple repeated cycles of 177Lu-octreotate in patients with recurrent neuroendocrine tumour. Eur J Nucl Med Mol Imaging. 2017 Jul;44(7):1207-1214. doi: 10.1007/s00259-017-3652-1. Epub 2017 Mar 1.

  PMID: 28246882 BACKGROUND

• Sabet A, Haslerud T, Pape UF, Sabet A, Ahmadzadehfar H, Grunwald F, Guhlke S, Biersack HJ, Ezziddin S. Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014 Feb;41(2):205-10. doi: 10.1007/s00259-013-2547-z. Epub 2013 Sep 13.

  PMID: 24030668 BACKGROUND

• van Essen M, Krenning EP, Kam BL, de Herder WW, Feelders RA, Kwekkeboom DJ. Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2010 Mar;51(3):383-90. doi: 10.2967/jnumed.109.068957. Epub 2010 Feb 11.

  PMID: 20150247 BACKGROUND

• Gleisner KS, Brolin G, Sundlov A, Mjekiqi E, Ostlund K, Tennvall J, Larsson E. Long-Term Retention of 177Lu/177mLu-DOTATATE in Patients Investigated by gamma-Spectrometry and gamma-Camera Imaging. J Nucl Med. 2015 Jul;56(7):976-84. doi: 10.2967/jnumed.115.155390. Epub 2015 May 21.

  PMID: 25999429 BACKGROUND

• Sundlov A, Sjogreen-Gleisner K, Svensson J, Ljungberg M, Olsson T, Bernhardt P, Tennvall J. Individualised 177Lu-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry. Eur J Nucl Med Mol Imaging. 2017 Aug;44(9):1480-1489. doi: 10.1007/s00259-017-3678-4. Epub 2017 Mar 22.

  PMID: 28331954 BACKGROUND

• Del Prete M, Buteau FA, Arsenault F, Saighi N, Bouchard LO, Beaulieu A, Beauregard JM. Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):728-742. doi: 10.1007/s00259-018-4209-7. Epub 2018 Nov 30.

  PMID: 30506283 BACKGROUND

• Deshayes E, Assenat E, Meignant L, Bardies M, Santoro L, Gourgou S. A prospective, randomized, phase II study to assess the schemas of retreatment with Lutathera(R) in patients with new progression of an intestinal, well-differentiated neuroendocrine tumor (ReLUTH). BMC Cancer. 2022 Dec 22;22(1):1346. doi: 10.1186/s12885-022-10443-4.

  PMID: 36550428 BACKGROUND

Related Links

• RCP
• HAS

MeSH Terms

Conditions

Neuroendocrine Tumors; Disease Progression

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Deshayes Emmanuel, PHD

  ICM Co. Ltd.

  STUDY CHAIR

Central Study Contacts

Moussion Aurore, MD

CONTACT

+33467612446; aurore.moussion@icm.unicancer.fr

Texier Emmanuelle

CONTACT

0467613102; emmanuelle.texier@icm.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It's a prospective, national, multicenter, open-label, randomized, phase II study, to compare 2 additional cycles of Lutathera® versus active surveillance in patients who already received two cycles of "Second PRRT" (already retreated with two cycles). Written informed consent will be collected before any study related procedures take place. Patients previously treated with 4 cycles of Lutathera® will be registered after a first progression (clinic, biologic and/or radiologic) of their neuroendocrine tumor.

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: July 8, 2021
• Study Start: October 18, 2021
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): October 1, 2031
• Last Updated: February 5, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (28)