This study will evaluate the potential immunomodulatory synergy of the association of metronomic cyclophosphamide (CMC) and interferon-alpha (IFN-alpha).

Inclusion Criteria:

• performance status ECOG-WHO ≤ 1
• histologically proved neuroendocrine tumor with Ki67 < or = 10%, metastatic or locally advanced without surgery possibility
• at least one measurable lesion based on RECIST criteria version 1.1
• signed written informed consent

Exclusion Criteria:

• previous treatment with interferon or cyclophosphamide
• treatment by immunosuppressive drugs
• diabetes complicated by coronary artery disease or vasculopathy
• severe respiratory failure, chronic respiratory failure, COPD
• history of severe heart failure
• severe renal or hepatic impairment
• diabetes complicated with coronary artery disease or vasculopathy
• alcoholism unweaned
• uncontrolled epilepsy and/or achievement of the central nervous system functions
• history of severe depressive syndrome
• presence or history of severe psychiatric condition, particularly severe depression, suicidal thoughts or attempted suicide
• decompensated liver cirrhosis
• severe myelosuppression
• psoriasis and sarcoidosis
• active disease condition or uncontrolled infection
• association with the yellow fever vaccine
• association with phenytoin in prophylaxis
• hypersensitivity against interferon or cyclophosphamide
• prior history of other malignancy except for: basal cell carcinoma of the skin, cervical intra-epithelial neoplasia and other cancer curatively treated with no evidence of disease for at least 3 years
• pregnancy, breast-feeding or absence of adequate contraception for fertile patients
• patients under guardianship, curatorship or under the protection of justice