A Phase II Trial of TAS-102 (Lonsurf) in Patients With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma After Progression Through First Line Chemotherapy

The primary objective is to evaluate the activity of TAS-102 in previously treated metastatic and locally advanced unresectable pancreatic cancer after progression through or intolerance to first line chemotherapy.

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