Neoplasms

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Gland and Hormone Related Diseases

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Neuroendocrine Tumors

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Endocrine Gland Neoplasms

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Neuroectodermal Tumors, Primitive

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Endocrine System Diseases

Neuroendocrine Tumor

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All Drugs and Chemicals

Lutetium Lu 177 dotatate

Radiopharmaceuticals

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

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

Lutathera

Moussion Aurore, MD

Texier Emmanuelle

Sylvie GIRAUD, MD

Paul SCHWARTZ, MD

Jean-Phillipe METGES, MD

Caroline MOREAU-TRIBY, MD

Elisabeth QAUK, MD

Anthony KELLY, MD

Côme LEPAGE, MD

Jean-Philippe VUILLEZ, MD

Amandine BERON, PR

Anne-Laure GIRAUDET, MD

David TAIEB, PR

Emmanuel DESHAYES, MD

Catherine ANSQUER, MD

Colette ZWARTHOED, MD

Charlotte LUSSEY, MD

Florence TENENBAUM, MD

Ghoufrane TLILI, MD

David TONNELET, MD

Frédéric Di FIORE, MD

Bruno MAUCHERAT, MD

Alessio IMPERIALE, PhD

Lawrence DIERICKX, MD

Elodie CHEVALIER, MD

Eric BAUDIN, MD

Deshayes Emmanuel, PHD

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.

The NETTER-1 clinical trial compared peptide receptor radionuclide therapy (PRRT) with \[177Lu\]Lu-DOTA-TATE (Lutathera®) every eight weeks (4 doses) plus 30 mg octreotide LAR every 4 weeks with high dose (60 mg) of octreotide LAR every 4 weeks in patients with progressive and unresectable midgut neuroendocrine well differentiated (G1, G2) tumors (NETs) with somatostatin-receptor positive imaging (SSTRi+). Lutathera® improves both median progression free survival (PFS) (28.4 months vs 8.5 months) and median overall survival (OS) ("not reached" vs 27.4 months) with a follow-up of 42 months. Lutathera® also has an impact on quality of life. Therefore, this treatment was approved by the European Medicines Agency and is now reimbursed in France in that specific indication. Despite these promising results, progression will occur in most of patients within a variable time with limited treatment options left. Retreatment with additional cycles of Lutathera® may be an option. Van der Zwan et al. showed in a large retrospective cohort (the "ROTTERDAM cohort") a median PFS of 14.6 months after retreatment with two additional cycles of PRRT with \[177Lu\]Lu-DOTA-TATE and a significant longer OS than in the non-randomized control group. Interestingly, the safety was similar in salvage group than in initial PRRT: no grade (G) 3/4 renal toxicity occurred and hematological toxicities were similar to the group of patients who received the initial treatment (4 cycles). In a smaller cohort of 15 patients, Yordanova et al. showed that 8 or more cycles of \[177Lu\]Lu-DOTA-TATE were well tolerated and led to a survival improvement. In this study, each salvage therapy consisted of 2 or 3 cycles. No severe (G3, G4) renal toxicity or G4 adverse event occurred. 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.

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.

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

A Prospective Randomized Phase II Study Assess the Schema of Retreatment With Lutathera® ([177LU]LU-DOTA-TATE) in Patients With New Progression of Intestinal Well-differenciated Neuroendocrine Tumor

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

Number and type of adverse event according to NCI-CTCAE v5.0.

the time from randomization until documented disease progression on radiological tumor assessment (as evaluated by an independent central review by radiologists blindly of the treatment assignments according to RECIST v1.1) or death from any cause, whichever occurs first

the time from randomization until death from any cause.

Quality of life will be measured by EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer, Quality-of-life questionnaire C30, no min and max values)

Quality of life will be measured by EORTC GI.NET21 questionnaire (European Organisation for Research and Treatment of Cancer, gastrointestinal neuroendocrine tumor, no min and max values)

Institut du Cancer de Montpellier - Val d'Aurelle

Spots Global Cancer Trial Database for intestinal well differentiated endocrine tumor