Phase Ib Multicenter, Cohort Dose Escalation Trial to Determine the Safety, Tolerance and Preliminary Antineoplastic Activity of Gemcitabine Administered in Combination With Continuous Intravenous Doses of PRI-724, a CBP/ β- Catenin Inhibitor, to Patients With Advanced or Metastatic Pancreatic Adenocarcinoma Eligible for Second-Line Therapy After Failing First-Line Therapy With FOLFIRINOX (or FOLFOX)
PRI-724 is a small molecule antagonist that binds to the co-activator CBP thereby
specifically inhibiting the subset of Wnt/β-catenin-driven genes that are up-regulated in
cancer cells. PRI-724 is being developed as a potential antineoplastic agent.
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum
tolerated dose (MTD) of sequential escalating doses per cohort of PRI-724 administered in
combination with gemcitabine to patients with adenocarcinoma of the pancreas that is locally
advanced, metastatic, or otherwise inoperable, who are candidates for second-line therapy
after failing first-line therapy with FOLFIRINOX (i.e., folinic acid [leucovorin],
fluorouracil, irinotecan, oxaliplatin)
- PRI-724: 320, 640, 905 mg/m2/day, continuous intravenous (CIV) infusion over 24 h,
daily × 7 days, 1 week on with 1 week recovery × 2 (4 weeks equals 1 cycle)
- Gemcitabine: 1000 mg/m2 IV over 30 minutes; 3 weeks on with 1 week recovery (4 weeks
equals 1 cycle)
Patients with documented, measurable or evaluable adenocarcinoma of the pancreas that is
locally advanced, metastatic, or otherwise inoperable, who are candidates for second-line
therapy after failing first-line therapy with FOLFIRINOX, will be entered into this phase
1b, multicenter, open-label, non-randomized, dose-escalation per cohort study. The trial is
designed to evaluate the safety, tolerability, DLT(s), and MTD of escalating doses of
PRI-724, a CBP/ β- catenin inhibitor, when administered in combination with a standard dose
of gemcitabine. Correlative studies include characterization of the PK profiles of PRI-724
and gemcitabine, evaluation of the utility of potential PD markers of PRI-724 activity, as
well as preliminary assessment of the antineoplastic activity of PRI-724 plus gemcitabine in
this patient population.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The Maximum Tolerated Dose (MTD) of PRI-724 + Gemcitabine measured by the number of dose limiting toxicities (DLTs) that occur.
If no DLT occurs in the first 3 patients of a cohort, the dose will be escalated to the next dose cohort. If 1 DLT occurs in the first 3 patients of a cohort, that cohort is expanded to 6 patients. If more than 1 DLT occurs in a 6 patient cohort, escalation is stopped & next lower dose is expanded to 12 patients to confirm the MTD.
18 months. DLTs will be measured as they occur throughout the patients' time on study.
Robert R. McWilliams, M.D.
United States: Institutional Review Board
|Mayo Clinic||Rochester, Minnesota 55905|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|Mayo Clinic Arizona||Scottsdale, Arizona 85259|
|Mayo Clinic Jacksonville, FL||Jacksonville, Florida 32224|