This study will enroll a total of 16 patients with advanced pancreatic cancer at Cedars-Sinai Medical Center. All subjects will receive combination therapy of gemcitabine, nab-paclitaxel, and L-glutamine. The study investigates what the appropriate dosage of L-glutamine is so that there is the lowest risk of side effects, and whether the supplement will make standard chemotherapy of gemcitabine and nab-paclitaxel more effective in treating advanced pancreatic cancer.

Inclusion Criteria:

1. Advanced or unresectable, histologically confirmed pancreatic cancer (new diagnosis or recurrent) referred to Cedars-Sinai Medical Center (CSMC), Samuel Oschin Comprehensive Cancer Institute (SOCCI) for first-line chemotherapy. Prior neoadjuvant or adjuvant chemotherapy and/or chemoradiation is allowed but must have been completed >6 months prior to recurrence.
2. Age ≥18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 or Karnofsky performance status ≥60%
4. Demonstrate adequate organ and marrow function (within 14 days of study treatment initiation)
5. Have measurable disease based on RECIST 1.1
6. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
7. Female subjects of childbearing potential should be willing to use adequate methods of birth control (hormonal or barrier method of birth control) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
8. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
9. Willingness to undergo serial peripheral blood draws and provide stool samples during predefined study timepoints and under prespecified conditions (i.e., fasted, morning blood collections).
10. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
2. Has previously received chemotherapy for metastatic disease (treatment with neoadjuvant or adjuvant therapy is allowed so long as progression occurred ≥6 months).
3. Has pre-existing grade ≥3 neuropathy.
4. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
5. Has a known hypersensitivity to any components of the study drugs.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
7. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
8. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
9. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
10. Has any gastrointestinal disorder (e.g., bowel obstruction) or neurologic condition (e.g., oropharyngeal dysphagia) that may result in impairment of oral intake and/or absorption of study drug in the opinion of the treating investigator.
11. Is currently receiving any parenteral nutrition or enteral (tube) feeding or is planning to use any other nutritional supplement during the study period.
12. Patients on strong CYP2C8 or CYP3A4 inhibitors or inducers within 1 week prior to starting nab-paclitaxel