Pancreatic Cancer
Conditions
Keywords
gemcitabine, nabpaclitaxel, advanced pancreatic cancer
Brief summary
This is a multi-institution, open-label, two-arm, prospective randomized controlled phase I trial with the purpose to investigate the clinical efficacy of combination gemcitabine, nab-paclitaxel, and L-glutamine compared to gemcitabine and nab-paclitaxel alone in treatment-naïve, unresectable or metastatic pancreatic cancer. This study hypothesizes that combining L-glutamine with gemcitabine and nab-paclitaxel represents a superior therapeutic strategy over gemcitabine and nab-paclitaxel alone in the first-line treatment of advanced PDAC based on the positive results of the phase I GlutaPanc trial that demonstrated the feasibility and preliminary efficacy of combining glutamine supplementation with gemcitabine and nab-paclitaxel in the first-line treatment of advanced PDAC. This study also plans to characterize the safety and secondary endpoints of efficacy (ORR and PFS) of the combination in this cohort. Additionally, the study will characterize the anti-cachexia effects of the study combination compared to control through standard measures such as weight gain, weight stability, and body composition assessments. Lastly, this study will conduct correlative studies on study treatment impact on tumor metabolism, the gut microbiome composition and bacterial metabolism, the plasma and fecal metabolome, and inflammatory signaling, relative to control, to identify potential biomarkers to guide selection of candidates ideal for L-glutamine-based combination therapy.
Interventions
1000 mg/m\^2 IV on D1, 8, and 15 of cycle
DRUGNab-paclitaxel
125 mg/m\^2 IV on D1, 8, and 15 of cycle
DRUGL-glutamine
0.3 g/kg oral BID
Sponsors
Jun Gong, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced or unresectable, histologically confirmed pancreatic ductal adenocarcinoma (PDAC, new diagnosis or recurrent, where recurrent tumor does not need to be histologically-confirmed) referred to Cedars-Sinai Medical Center (CSMC), Samuel Oschin Comprehensive Cancer Institute (SOCCI), USC, or UC Irvine for first-line chemotherapy. Prior neoadjuvant or adjuvant chemotherapy and/or chemoradiation is allowed but must have been completed ≥6 months prior to recurrence. * Age ≥18 years * ECOG performance status ≤2 or Karnofsky performance status ≥60% * Demonstrate adequate organ and marrow function * Have measurable disease based on RECIST 1.1 * Female subject of childbearing potential should have a negative urine or serum pregnancy within 14 days prior to receiving the first dose of study medication for eligibility verification. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: Negative urine or serum pregnancy test is also conducted within 72 hours prior to C1D1 for study procedures and should not preclude eligibility verification, but if screening pregnancy test is done within 72 hours of C1D1, it is not required to be repeated. * 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. * 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. * Willingness to provide baseline tissue, stool, and blood samples under prespecified conditions (i.e., fasted, morning blood collections) * Must be willing to provide repeat stool and blood samples after 1-week lead-in (±3 day window) and optional post-progression tumor biopsy * Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
Exclusion criteria
* 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. * Has previously received chemotherapy for metastatic disease (treatment with neoadjuvant or adjuvant therapy is allowed so long as treatment was completed ≥6 months prior to recurrence). * Has pre-existing grade ≥3 neuropathy. * 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. * Has a known hypersensitivity to any components of the study drugs. * 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. * 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. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * 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. * 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. * Patients on strong CYP2C8 or CYP3A4 inhibitors or inducers within 1 week prior to starting nab-paclitaxel (Appendix X).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 2 years post End of Treatment | To determine the clinical efficacy of L-glutamine supplementation with gemcitabine and nab-paclitaxel to gemcitabine and nab-paclitaxel alone in the first-line treatment of advanced pancreatic cancer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 2 years post End of Treatment | — |
| Objective Response Rate (ORR) | 2 years post End of Treatment | — |
| Safety based on NCI CTCAE Version 5.0 | 2 years | — |
| Weight change | Up to 12 weeks | Weight gain, as measured by the change in body weight from baseline to 12 weeks of study treatment |
| Weight stability | up to 12 weeks | Weight stability, as defined by weight change less than 0.1 kg/baseline body mass index (BMI)-unit) at 12 weeks of study treatment |
| Body composition | at first follow-up CT scan, around 8 weeks post cycle 1 day 1 (each cycle is 28 days) | Body composition assessment, as measured by the difference between baseline skeletal muscle index (SMI) or adipose tissue index (ATI) and the SMI or ATI calculated at first follow-up CT scan |
Countries
United States
Contacts
CONTACTJun Gong, MD
PRINCIPAL_INVESTIGATORJun Gong, MD
Cedars-Sinai Medical Center
Outcome results
None listed