Assessment of the Schema of Retreatment With Lutathera® in Patients With New Progression of Intestinal Well-differenciated Neuroendocrine Tumor

• Status: Not yet recruiting
• Trial end date: 2029-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Treatments: Lutetium Lu 177 dotatate

Criteria

Inclusion Criteria:

• 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,

• Somatostatin receptor imaging positive imaging (SSTRi+) disease within 4 months prior to randomization: (may be PET imaging (68Ga-based SSTR analogues) or scintigraphy imaging: 111In-pentetreotide or 99mTc-octreotide. At least 90% of lesions must be positive for SSTRi with a significant uptake (>= liver of surrounding tissue),

• 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),

• Negative pregnancy test in women of childbearing potential (the β-HCG dosage must be ≤ 4 days before inclusion). Women who have no reproductive potential are postmenopausal women or women who have had permanent sterilization, eg. tubal occlusion, hysterectomy, bilateral salpingectomy),

• 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

Exclusion Criteria:

• 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 (measured 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,

• Concomitant participation or participation within the last 30 days in another clinical trial,

• History of other solid tumor in 5 years before the inclusion excepted of cancer in situ of the cervix and skin cancer (basal or squamous cell) treated and controlled.

• Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study.