Clinical Trial · NCT06045260

"Receptor Radionuclide Therapy With 177Lu-DOTATOC

Overview

Peptide receptor radionuclide therapy (PRRT) may be recommended in G1- G2 GEP-NET patients with disease progression on somatostatine analogues therapy (LUTATHERA®). However, there are several diseases, including neuroendocrine neoplasia not originating from the digestive tract, for which the efficacy of PRRT has already been demonstrated, but which are not currently within the indications of LUTATHERA and therefore cannot benefit from it (i.e. bronchopulmonary, ovarian, renal NETs and neuroendocrine carcinomas). Moreover, the role of PRRT is also accepted in Pheochromocytomas and paragangliomas (PPGLs), Meningiomas, but also as a salvage therapy in pre-treated NET pts, and other SSTR-positive malignancies (Lymphomas, Gliomas…). Least explored among radiopharmaceuticals for SSTR-positive tumors is 177Lu-DOTATOC. This study aims to investigate the efficacy and safety of lutetium (177Lu) edotreotide (Lu-Dotatoc) on all the above-mentioned diseases that could benefit from receptor radionuclide therapy. We believe that this study, which will involve only patients outside the indication of LUTATHERA, will expand the current knowledge of radionuclide receptor therapy with 177Lu- DOTATOC, particularly with regard to objective response and safety parameters, and may consolidate its in the management of these diseases.

Sponsor

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Phase

Phase 2

Contacts

Federica Matteucci (PRINCIPAL_INVESTIGATOR)

Oriana Nanni (CONTACT)

oriana.nanni@irst.emr.it

+390543739266

Bernadette Vertogen (CONTACT)

bernadette.vertogen@irst.emr.it

+390544286058

Maddalena Sansovini (STUDY_CHAIR)

ClinicalTrials.gov

NCT06045260

Drug / Compound

DOTATOC

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

Eligibility

Inclusion

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 \> 50 ml/min.
Measurable disease according to RECIST 1.1 criteria also patients without measurable but with evaluable disease can be enrolled.
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.
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.
Life expectancy of greater than 6 months.
Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed.
ECOG performance status \<2.
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.
If female of childbearing potential highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials", (2014\_09\_15 section 4.1) 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. A negative serum pregnancy test should be performed the same day the treatment is started at any cycle. 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 (see Appendix F).

Exclusion

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 ≤ 1 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.
Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective aminoacids given concurrently with the lutetium (177Lu) edotreotide infusion;
Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA or components of the formulation or other radiolabeled peptide agents.
Patients which are included in the indication of LUTATHERA®(9).
Pregnant or breastfeeding women are excluded from the present study.
Patients treated with prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow.
Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy.
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.
ECOG performance status \>2.