Study Evaluating the Ketogenic Diet in Patients with Metastatic Pancreatic Cancer

Inclusion Criteria:

1. Age ≥ 18 years of age; male or female.

2. Histologically or cytologically confirmed metastatic pancreatic ductaladenocarcinoma, not previously treated for their metastatic disease.

3. Capable of providing informed consent and complying with trial procedures.

4. Karnofsky Performance Status (KPS) of ≥ 70%.

5. Life expectancy ≥ 12 weeks.

6. Measurable tumor lesions according to RECIST 1.1 criteria.

7. <Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0.

8. Patient has acceptable coagulation status as indicated by an INR ≤1.5 timesinstitutional upper limit of normal (ULN). Patients on anticoagulation can beincluded at the discretion of the investigator.

9. Patients must have normal organ and marrow function as defined below:

• Absolute neutrophil count ≥1,500/mm3

• Platelet concentration ≥100,000/mm3 with no platelet transfusions within 7 daysprior to laboratory sample

• Hemoglobin ≥ 9.0g/dL (PRBCs may be given to meet this criteria)

• Hematocrit level ≥ 27%

• Total bilirubin within 1.25 x ULN

• AST (SGOT) and ALT (SGPT) ≤ 2.5 times upper limit of normal (if livermetastases are present, then ≤ 5 x ULN is allowed)

• Serum creatinine < 1.5 mg/dL.

10. Patient must have a Smartphone or computer in order to work with Virta

11. Females of child-bearing potential (defined as a sexually mature woman who (1) hasnot undergone hysterectomy [the surgical removal of the uterus] or bilateraloophorectomy [the surgical removal of both ovaries] or (2) has not been naturallypostmenopausal for at least 24 consecutive months [i.e., has had menses at any timeduring the preceding 24 consecutive months]) must:

12. Either commit to true abstinence* from heterosexual contact (which must bereviewed on a monthly basis), or agree to use, and be able to comply with,effective contraception without interruption, 28 days prior to starting IPtherapy (including dose interruptions), and while on study medication or for alonger period if required by local regulations following the last dose of IP;and

13. Have a negative serum pregnancy test (β -hCG) result at screening and agree toongoing pregnancy testing during the course of the study, and after the end ofstudy therapy. This applies even if the subject practices true abstinence* fromheterosexual contact.

14. Male subjects must practice true abstinence* or agree to use a condom during sexualcontact with a pregnant female or a female of childbearing potential whileparticipating in the study, during dose interruptions and for 6 months followingdiscontinuation from study treatment, even if he has undergone a successfulvasectomy.

• True abstinence is acceptable when this is in line with the preferred and usuallifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation,symptothermal, post-ovulation methods) and withdrawal are not acceptablemethods of contraception].

Exclusion Criteria:

1. Patients must have received no previous radiotherapy, surgery, chemotherapy orinvestigational therapy for the treatment of their metastatic pancreatic disease.Prior treatment in the adjuvant setting with chemotherapy and radiation are allowed,provided at least 6 months have elapsed since completion of the last therapy andrecurrence and no lingering toxicities are present (this will be first linetreatment for metastatic disease).

2. Evidence of central nervous system (CNS) metastasis (negative imaging study, ifclinically indicated, within 4 weeks of Screening Visit).

3. History of other malignancies (except cured basal cell carcinoma, superficialbladder cancer or carcinoma in situ of the cervix) unless documented free of cancerfor ≥ 2 years.

4. Uncontrolled intercurrent illness, including but not limited to New York HeartAssociation Class III or IV, myocardial infarction within the past 6 months, orunstable arrhythmia.

5. Known infection with HIV, hepatitis B, or hepatitis C.

6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systematictherapy.

7. Major surgery within 4 weeks prior to study entry. (Port-a-cath may be insertedduring this time period).

8. Any condition in the opinion of the principal investigator that might interfere withthe patient's participation in the study or in the evaluation of the study results.

9. Any condition in the opinion of the principal investigator that is unstable andcould jeopardize the patient's participation in the study.

10. Unwillingness or inability to comply with procedures required in this protocol,including unwillingness to follow a ketogenic diet.

11. Severe malnutrition or body mass index (BMI) < 18.

12. Albumin < 3.0 g/dL.

13. History of Type 1 diabetes.

14. History of diabetic ketoacidosis (DKA).