TAS-102 in Extrapulmonary Neuroendocrine Carcinoma

Prior treatment

• Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38°C).
• Taking other investigational or anti-cancer treatments while participating in this study. Concurrent radiotherapy is allowed provided to non-target lesions. If target lesions have received radiation therapy, progression must have been demonstrated prior to enrollment.
• Prior or concurrent malignancy, except for the following: a) Adequately treated basal cell or squamous cell skin cancer; b) Cervical carcinoma in situ; c) Adequately treated Stage I or II cancer from which the subject is currently in complete remission; d) Or any other cancer from which the subject has been disease-free for 3 years.

Other illness

• Known pulmonary primary or small cell lung cancer will be excluded.
• Significant or uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias within the last six months.
• Other severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as: a) Severe impaired lung functions as defined by spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air, b) Uncontrolled diabetes,c) Liver disease such as cirrhosis or severe hepatic impairment, d) Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the integrity of the study.

Other

• Women who are pregnant or breastfeeding.
• Evidence of low-grade or well-differentiated features as determined by the investigator.
• Functional neuroendocrine tumors are excluded.

• Pathologic confirmation of high grade NEC using WHO criteria as determined by Ki67>20%, poorly differentiated (G3) characteristics, or >20 mitotic figures/10 high-power fields.
• Unknown primary may be included. Suspected extrapulmonary patients with known lung primary will be excluded.
• Prior treatment with a platinum containing regimen
• RECIST 1.1 measurable disease
• Evidence of stage IV, metastatic disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Serum albumin ≥2.5 gm/dL.
• Expected survival ≥3 months.
• Adequate hematologic function as defined by: a) Absolute neutrophil count (ANC) >1500/mm3; b) Platelets ≥75,000/mm3; c) Hemoglobin >8 g/dL (in the absence of red blood transfusion).
• Adequate liver function, as defined by: a) Serum total bilirubin ≤2.5 x ULN mg/dL. b) ALT (SGPT) and AST (SGOT) ≤5 x upper limit of normal (ULN).
• Adequate renal function, as defined by serum creatinine ≤2.0 x ULN, or creatinine clearance ≥30 mL/min
• Females of child bearing potential must agree to use contraception to avoid pregnancy throughout the study.