TAS-102 (Lonsurf) in Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma Post First Line Chemotherapy (UF-STO-PANC-003)

Inclusion Criteria:

- Histologic or cytologic confirmed adenocarcinoma of the pancreas.

- Clinically metastatic or locally advanced unresectable disease as verified by
radiographic imaging. Subjects without clear evidence of distant metastatic disease
will be presented at multidisciplinary tumor board for discussion of disease
resectability.

- Documented progression or intolerance to first or second line chemotherapy which was
prescribed for metastatic pancreatic adenocarcinoma or locally advanced unresectable
disease. Intolerance is defined as any sign or symptom from chemotherapy that resulted
in stopping the chemotherapy treatment prematurely before progression of disease or
the subject's desire to stop treatment without evidence of progression.

- TAS102 will be planned to start after disease progression on first-or second line
chemotherapy, provided any prior chemotherapy-related toxicities have resolved to less
than or equal to Grade 1 or baseline within 28 days of the date the subject signs the
informed consent form. Grade 2 or greater toxicities including alopecia, skin
pigmentation,and platinum induced neurotoxicity/neuropathy are acceptable for starting
on trial, as these toxicities do not preclude treatment with TAS102

- ECOG Performance Status of 0-2

- Capacity to understand and sign the informed consent document

- Able to take medications orally

- Life expectancy > 12 weeks as predicted by the treating oncologist's clinician
judgement

- Age >18 years

- Patients of childbearing potential must be using an effective means of contraception
including but not limited to barrier methods, birth control, intrauterine devices.

Histologic diagnosis of pancreatic cancer that has been treated previously with one or two
lines of chemotherapy.

Previous surgery and/or radiotherapy may have been performed up to 4 weeks prior to the
date the subject signs the informed consent form, but there must be evidence of disease
progression radiographically or intolerance to first or second-line chemotherapy.

Patients on anticoagulation need to have no evidence of bleeding and be on a stable
anticoagulation dose for at least 2 weeks prior to the date the subject signs the informed
consent form.

- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for at least 6 months after
the last dose of study drug to minimize the risk of pregnancy. Prior to signing the
informed consent form, women of childbearing potential must be advised of the
importance of avoiding pregnancy during trial participation and the potential risk
factors for an unintentional pregnancy.

- WOCBP include any woman who has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:

- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or

- For women with irregular menstrual periods who are taking hormone replacement
therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of
greater than 35 mIU/mL.

- Males with female partners of child-bearing potential must agree to use
physician-approved contraceptive methods (e.g., abstinence, condoms,
vasectomy) throughout the study and should avoid conceiving children for 3
months following the last dose of study drug.

- Subjects must have provided written informed consent and be willing to
comply with all study-related procedures.

- Baseline laboratory values (bone marrow, renal, hepatic) must include:

- Adequate bone marrow function:

1. Absolute neutrophil count >1500/µL

2. Platelet count >75,000/µL

3. HGB equal to or greater than 7g/dL

- Renal function:

a. Serum creatinine ≤ 1.5 mg

- Hepatic function:

1. Total bilirubin ≤ 1.5 mg/dL

2. AST and ALT equal to or less than 3 times the upper limit of normal

3. Serum calcium ≤ 12 mg/dl

Exclusion Criteria:

- Pregnant or lactating females

- Decline using effective means of contraception if sexually active

- Previously taken TAS-102

- Myocardial infarction or ischemia within the 6 months before study screening

- Uncontrolled' clinically significant dysrhythmia

- No history of an invasive malignancy within the five years prior to initiating therapy
on this protocol. Patients may have prior in situ carcinomas (such as of the breast or
cervix), non-melanoma skin cancers, Rai Stage 0 chronic lymphocytic leukemia or
monoclonal gammopathy of uncertain significance and still otherwise qualify for
enrollment on this protocol

- Radiotherapy to the target lesion within 2 weeks of the date the subject signs the
informed consent form

- Major surgery within 4 weeks of the date the subject signs the informed consent form
(the surgical incision should be fully healed prior to study medication
administration).

- Antineoplastic, biologic or anti-cancer treatment within prior 3 weeks. A 3 week
washout period will be required prior to beginning study treatment if subjects have
received anti-cancer treatment within this time frame.

- Lingering NCI-CTCAE toxicity grade 2 or higher from prior cancer treatments (excluding
alopecia, skin pigmentation, and platinum induced neurotoxicity) > 28 days after the
date the subject signs the informed consent form

- Any co morbid condition that' in the view of the attending physician' renders the
patient at high risk from treatment complications including but not limited to chronic
infections, uncontrolled diabetes, congestive heart failure according to the NYHA
criteria, untreated brain metastases, liver or renal failure, gastrointestinal
hemorrhage.

- Patients with severe hepatic enzyme impairment manifesting as total bilirubin greater
than 1.5 mg/dL or greater than 3 times the upper limit of normal of AST or ALT

- Known brain metastases or leptomeningeal disease

- Active infection (i.e., body temperature > or equal to 38-degrees C due to infection)

- Other concurrently active malignancies excluding malignancies that are disease free
for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment.

- Prisoners or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical illness.

- Subjects demonstrating an inability to comply with the study and/or follow-up
procedures