Octreotide LAR in the Induction of Immunologic Response in NENs Patients

MDSCs and T-Regs will be evaluated at baseline pre-treatment with octreotide, after 15 days, at three and at six months and before each octreotide LAR administration for 12 months. MDSC cells will be detected by surface receptors LIN-, CD11b, CD14, CD15, CD33, CD124-IL4-Ra, CD184-CXCR4, CD279-PD1, HLA-DR and T-reg cells from CD3, CD4, CD8 receptors , CD25, CD39, CD45RA, CD45R0, CD62L, CD127, CD152-CTLA-4, CD184-CXCR4, CD278-ICOS, CD279-PD-1. Briefly, CD4 + cells will be separated by negative selection, using the mixture of human CD4 antibodies. Octreotide is currently a registered drug to the FDA, EMA and AIFA with the indication for the treatment of well and moderately differentiated NETs functioning and not working on the front line. .

• Octreotide Acetate (Drug), also known as Somatostatin analog: administration every 28 days

Primary outcomes

• Exploring the changes in immune-regulatory cells induced by OCT LAR [6 months]: The primary objective of the project is to evaluate changes in immune-regulatory cells induced by OCT LAR from baseline to month 6. Therefore, we will observe the impact of OCTREOTIDE LAR on the immune response by studying T-Reg and MDSC and the immunoregulatory cell population in peripheral blood of patients with neuroendocrine tumors G1 / G2 treated with OCT LAR.

Secondary outcomes

• Outcome [3 months (PFS - ORR)]: Objective response rate according to RECIST. Progression-free survival (PFS), defined as the time (days) from start date of octreotide to date of first documented disease progression or death due to any cause, if death occurs before progression is documented. Progression-free survival as the time (days) from start date of OCT to date of first PD or death due to any cause; Safety :number of patients presenting AE during treatment and observation period (CTCAE v.4)
• safety assessment [1 month (safety)]: Safety profile according to CTCAE criteria

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Signed informed consent prior to initiation of any study-specific procedures or treatment, as confirmation of the patients awareness and willingness to comply with the study requirements.
* Patients ≥18 years of age.
* Patients with histologically confirmed well and moderately differentiated Neuroendocrine Tumors with Ki67 ≤ 20% (Ki67 must be quantified in percentage) and candidates for treatment with octreotide.
* ECOG performance status (PS) of 0-2.
* At least 28 days since prior the last radiation therapy or surgery.
* Estimated life expectancy of ≥12 weeks.

Exclusion Criteria:

* Patients < 18 years of age.
* According to the current SmPC of the prescribed drug agent.
* Previuos treatment with octreotide.
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would prevent the patient from meeting the study requirements.
* Serious active infection requiring i.v. antibiotics and/or hospitalization at study entry.
* Patients who are treated with any medicinal product that contraindicates the use of the study drug, may interfere with the planned treatment, affects patient compliance or puts the patient at high risk for treatment-related complications.
* Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. Women of childbearing potential (defined as inferior to 2 years after last menstruation and not surgically sterile) not using effective, non hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
* Patients with meningeal carcinomatosis
* Patients with known positive HIV status

• Salvatore Tafuto, MD, Principal investigator, NCI Naples