Study 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.
Eligibility
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 inclusion : (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 (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,
* 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.
