CPI-613 (Devimistat) in Combination With Chemoradiation in Patients With Pancreatic Adenocarcinoma

Inclusion Criteria

• •1. Age ≥ 18 years.
• •2. Pathologically confirmed (histologic or cytologic) adenocarcinoma of the pancreas.
• •3. Patients should have an inoperable disease (locally advanced, oligometastatic, or medically inoperable) and, based on the review of the institutional pancreatic tumor board, should otherwise benefit from chemoradiation for definitive local control of the primary tumor.
• •4. Patients with and without regional adenopathy are eligible.
• •5. History/physical examination, including a collection of weight and vital signs, within 30 days prior to treatment.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 14 days of study entry.
• •7. Imaging requirements are to include
• •1. Diagnostic abdominal/pelvic CT with IV contrast or abdominopelvic magnetic resonance (MR) scan with perfusion and diffusion-weighted sequences within 45 days prior to study entry.
• •2. Chest CT scan or X-ray within 45 days prior to study entry.
• •3. Radiation treatment planning abdominal CT. A recommended abdominal MR will be done as a simulation (SIM) scan with interpretation. The CT SIM will not be done with interpretation. Positron emission tomography (PET) scan and MRI are both optional but encouraged. Abdominal MR scans for staging and radiation planning and follow-up are optional but encouraged.
• •8. Heme Onc (Chem 24) and cancer antigen 19-9/ carcinoembryonic antigen (CEA) within 30 days prior to treatment, as follows:
• •1. Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3.
• •2. Platelets ≥ 100,000 cells/mm3.
• •3. Hemoglobin ≥ 8.0g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dl is acceptable).
• •4. Not on hemodialysis.
• •5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \<4x the upper limit of normal.
• •6. Total bilirubin \<2x the upper normal mg/dL (higher levels are acceptable if Gilbert Syndrome is suspected clinically).
• •9. Negative serum pregnancy test (if applicable).
• •10. Ability to position for radiation therapy.
• •11. Pregnancy It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
• •Female patients must meet one of the following:
• •* Postmenopausal for at least one year before the screening visit, or
• •* Surgically sterile, or
• •* If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through three months after the last dose of study drug, and
• •* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or
• •* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.)
• •Male patients, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following:
• •* Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, or
• •* Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or
• •* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)
• •12. Ability to understand a written informed consent document, and the willingness to sign it.