Receptor radionuclide therapy with 177Lu-DOTATOC (177Lu- edotreotide or 177Lu-octreotide) in SSTR positive patients: a multicenter, prospective, phase II trial

Prior treatment

• Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy
• Patients treated with prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow
• Patients treated with previous PRRT with an absorbed dose to the kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of dosimetry (13)
• All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE)
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening

Other illness

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA or components of the formulation or other radiolabeled peptide agents
• Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective aminoacids given concurrently with the lutetium (177Lu) edotreotide infusion

Other

• Pregnant or breastfeeding women are excluded from the present study
• Patients which are included in the indication of LUTATHERA®
• ECOG performance status >2

• Age ≥18 years
• A female participant is eligible to participate if she is not pregnant and not breastfeeding. If female of childbearing potential highly effective birth control methods, according to guideline “Recommendation related to contraception and pregnancy testing in clinical trials” are mandatory (see Appendix F). Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required ( established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg., bilateral orchiectomy), for more than 6 months
• Participant is willing and able to give informed consent for participation in the study.
• Patients must have histologically or cytologically confirmation of neuroendocrine tumors or any other tumor histology type documented as sst2-positive, that may benefit from receptor radionuclide therapy and for which there are not any other effective treatments, included locoregional methods of control for PPGLs/pheochromocytoma. For cerebral and PPGLs sst2-positive tumors, if biopsy is no feasible for technical reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the 68Ga PET-CT dota-peptide SSTr2 positivity
• Measurable disease according to RECIST 1.1 criteria also patients without measurable but with evaluable disease can be enrolled
• Any disease stage is allowed. Patients with documented disease will be admitted to the therapeutic phase only if the diagnostic PET/CT 68Ga-peptide images demonstrate a significant uptake in the tumour, according to the adapted Krenning Scale. Only patients with a greater caption (Grade 3 or 4) in most of the lesions will be admitted
• Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed
• Patients with or without concurrent therapy with somatostatin analogs. It will be maintained the same dose of the SSA analogs as at the time of demonstrated disease progression
• Life expectancy of greater than 6 months
• ECOG performance status ≤2
• Adequate haematological, liver and renal function: haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109 /L; platelets ≥ 100 x 109 /L; bilirubin ≤1.5 X UNL (upper normal limit), ALT and AST <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL and/or eGFR or creatinine clearance ≥ 45 ml/min