Tamoxifen for the Treatment of Hormone Receptor Positive, Well Differentiated Neuroendocrine Tumors, the HORMONET Study

Inclusion Criteria

• Histological diagnosis of well differentiated NET, advanced / metastatic, inoperable, with no possibility of curative treatment
• Immunohistochemistry expression >= 1% for the estrogen and/or progesterone receptor
• A disease with radiological progression (at least 10% of tumor growth) in the last 12 months before cycle 1 day 1 (C1D1)
• Progression on somatostatin analog as well as progression/intolerance with additional systemic therapy if somatostatin/receptor positive, and progression/intolerance after at least one systemic line of treatment if somatostatin receptor negative. Pancreatic NET patients must have received at least two lines of systemic therapy regardless of somatostatin receptor expression
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) performance scale 0 to 2
• Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) =< 2.5 times the upper limit of local laboratory normality (ULN-LL); (up to 5 x upper limit of normal [ULN] for patients with liver metastases)
• Total serum bilirubin =< 2.0 x ULN-LL
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 80,000/mm^3
• Hemoglobin >= 9.0 g/dL
• Estimated creatinine clearance per the Cockcroft-Gault equation >= 30 mL/min or serum creatinine < 1.5 x upper limit of normal (ULN)
• Albumin >= 3.5 g/dL
• Institutional normalized ratio (INR) =< 1.5
• Informed consent form signed by the patient or legal representative

Exclusion Criteria

• Patients with prior exposure to tamoxifen
• Patients with an aggressive disease requiring cytotoxic therapy or locoregional therapies (e.g., hepatic embolization)
• A history of serious clinical or psychiatric illness that, by clinical judgment, may involve risk due to participation in this study
• Patients participating in other protocols with experimental drugs
• Patients having difficulties with ingesting food orally
• Patients who have recently undergone major surgery, less than 4 weeks ago
• Patients receiving chemotherapy or other oncological therapy within 3 weeks of cycle 1 day 1
• Patients who use oral anticoagulation
• Previous history of deep vein thrombosis or pulmonary embolism in the last 12 months
• Pregnant or lactating patients
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 30 days after the last dose of study medication. Female patients are considered to be of non-reproductive potential if they are either postmenopausal (at least 12 months with no menses without an alternate medical cause), have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion, or have a congenital or acquired condition that prevents childbearing. Appropriate methods of birth control include: abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
• Male subjects of childbearing potential and/or who are sexually active with a female of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 30 days after the last dose of study medication. Male subjects are considered to be of non-reproductive potential if they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition). Appropriate methods of birth control include: abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
• Patients with post-menopausal vaginal bleeding with no defined etiology
• Patients with breast cancer who need to use tamoxifen for this neoplasm
• Another synchronous neoplasm that demands systemic treatment