Peptide Receptor Radionuclide Therapy (PRRT) in Tumors With High Expression of Somatostatin Receptors (Phase 2)

The rationale behind the purpose of this study lays on: * the evidence that PRRT could represent a valuable treatment for the majority of patients with neuroendocrine tumor (NET) in disease progression, operated or inoperable, presenting lesions expressing somatostatin receptors and for which standard treatments are not already available; * the current impossibility of acquiring on the market radiolabelled analogues of somatostatin used for PRRT with marketing authorisation; * the need to collect a larger case history than in previous studies; * the need to stratify the various histotypes based on the response obtained; * the need to define new treatment schemes that guarantee the maximum efficacy and the lowest possible toxicity - with low cumulative (and per cycle) activities radiopharmaceutical and according to the concept of dose hyperfractionation - with a view to an optimal balance between risk and benefit.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 1\. Age ≥18 years, of both sexes, of any ethnicity;
* 2\. Cyto-histological and immunohistochemical diagnosis of NET;
* 3\. Evaluation of the cell proliferation index by studying Ki-67 and / or E3 ubiquitin-protein ligase (MIB-1).
* 4\. Illness measurable according to RECIST 1.1 criteria by imaging conventional (CT with contrast medium or MRI with contrast medium) not earlier than two months with respect to enrollment;
* 5\. Elevated expression of somatostatin receptors documented by PET-CT with 68Ga-DOTATOC in the target lesion (s). It is defined as "high expression of somatostatin receptors "a ratio of Maximum standardized uptake value (SUVmax) lesion / Mean standardized uptake value (SUVmean) muscle ≥ 4: 1 calculated with semi-quantitative analysis on examination PET-CT with 68Ga-DOTATOC;
* 6\. Dosage of Chromogranin A (and any other specific markers) not prior to two months of enrollment;
* 7\. Evaluation of glucose metabolism in the target lesion (s) by PET-CT with 18F-FDG;
* 8\. Preserved haematological, hepatic and renal parameters, in particular: white blood cells ≥2500 / μL; platelets ≥ 90000 / μL; hemoglobin ≥ 9 gr / dL; creatinine ≤ 2 mg / dL; bilirubin ≤ 2.5 mg / dL
* 9\. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
* 10\. Life expectancy ≥ 6 months;
* 11\. Stable or progressive disease, at any stage, both in operated patients that inoperable;
* 12\. Absence of standard treatments already documented and of equal effectiveness;
* 13\. Absence of surgical, chemotherapy and / or radiotherapy treatments for at least 30 days. On the other hand, patients in therapy with somatostatin analogues or biologics, such as mechanistic target of rapamycin (m-TOR) inhibitors;
* 14\. Voluntary participation in the study by signing the consent form informed, after reading and complete understanding of the information notes.

Exclusion Criteria:

* 1\. Lack of the requirements listed above;
* 2\. State of pregnancy;
* 3\. Breastfeeding and relative refusal to suspend breastfeeding;
* 4\. Participation in another therapeutic experimental clinical protocol in the four weeks prior to the PRRT;
* 5\. Bone marrow invasion of disease\> 25% confirmed;
* 6\. Previous extensive radiotherapy treatments.

• BACKGROUNDSmit Duijzentkunst DA, Kwekkeboom DJ, Bodei L. Somatostatin Receptor 2-Targeting Compounds. J Nucl Med. 2017 Sep;58(Suppl 2):54S-60S. doi: 10.2967/jnumed.117.191015. PMID 28864613
• BACKGROUNDModlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003 Feb 15;97(4):934-59. doi: 10.1002/cncr.11105. PMID 12569593
• BACKGROUNDTeunissen JJ, Kwekkeboom DJ, Valkema R, Krenning EP. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer. 2011 Oct 17;18 Suppl 1:S27-51. doi: 10.1530/ERC-10-0282. Print 2011 Oct. PMID 22005114
• BACKGROUNDYao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20;26(18):3063-72. doi: 10.1200/JCO.2007.15.4377. PMID 18565894
• BACKGROUNDHemminki K, Li X. Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer. 2001 Oct 15;92(8):2204-10. doi: 10.1002/1097-0142(20011015)92:83.0.co;2-r. PMID 11596039
• BACKGROUNDModlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008 Jan;9(1):61-72. doi: 10.1016/S1470-2045(07)70410-2. PMID 18177818
• BACKGROUNDKloppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M, Rindi G, Plockinger U; Mallorca Consensus Conference participants; European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology. 2009;90(2):162-6. doi: 10.1159/000182196. Epub 2009 Aug 28. No abstract available.