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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
146
2 additional infusions of Lutathera®
Institut de Cancérologie de l'Ouest Site d'Angers
Angers, France
RECRUITINGInstitut Bergonié
Bordeaux, France
RECRUITINGCHRU Morvan
Brest, France
RECRUITINGHospices civils de LYON - GHE
Bron, France
RECRUITINGCentre François Baclesse
Caen, France
RECRUITINGCH Métropole de Savoie
Chambéry, France
RECRUITINGCentre Jean Perrin
Clermont-Ferrand, France
RECRUITINGHopital Beaujon
Clichy, France
RECRUITINGCHU de DIJON
Dijon, France
RECRUITINGCHU Grenoble Alpes (CHUGA)
La Tronche, France
RECRUITING...and 18 more locations
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.
Time frame: assessement every cycle (every 8 weeks) 6 months from randomization
Evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance in term of Safety
Number and type of adverse event according to NCI-CTCAE v5.0.
Time frame: 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 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
Time frame: 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 from randomization until death from any cause.
Time frame: the time without death during 5 years after the treatment
To assess quality of life of general patient
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)
Time frame: 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
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)
Time frame: 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
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