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Updated: Dec 20, 2025
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
A Phase II, Single-Arm, Open-Label, Bayesian Adaptive Efficacy and Safety Study of PBI-05204 in Patients with Stage
Marc T Roth1, Dana Backlund Cardin1, Erkut Hasan Borazanci2
1Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
Lessons Learned:
This trial evaluating a novel plant extract, PBI-05204, did not meet its primary endpoint of overall survival but did show signals of efficacy in heavily pretreated mPDA. PBI-05204 was generally well tolerated, with the most common side effects related to treatment being vomiting (23.7%), nausea (18.4%), decreased appetite (18.4%), and diarrhea (15.8%). Additional trials are needed to explore the role of PBI-05204 in cancer treatment.
Background:
Survival for metastatic pancreatic ductal adenocarcinoma (mPDA) is dismal, and novel agents are needed. PBI-05204 is a modified supercritical carbon dioxide extract of Nerium oleander leaves. Oleandrin, the extract's major cytotoxic component, is a cardiac glycoside that has demonstrated antitumor activity in various tumor cell lines with a mechanism involving inhibition of Akt phosphorylation and through downregulation of mTOR.
Methods:
A phase II, single-arm, open-label study to determine the efficacy of PBI-05204 in patients with refractory mPDA therapy was conducted. The primary endpoint was overall survival (OS), with the hypothesis that 50% of patients would be alive at 4.5 months. Secondary objectives included safety, progression-free survival (PFS), and overall response rate. Patients received oral PBI-05204 daily until progressive disease (PD), unacceptable toxicity, or patient withdrawal. Radiographic response was assessed every two cycles.
Results:
Forty-two patients were enrolled, and 38 were analyzed. Ten patients were alive at 4.5 months (26.3%) with a median PFS of 56 days. One objective response (2.6%) was observed for 162 days. Grade ≥ 3 treatment-emergent adverse events occurred in 63.2% of patients with the most common being fatigue, vomiting, nausea, decreased appetite, and diarrhea.
Conclusion:
PBI-05204 did not meet its primary endpoint for OS in this study. Recent preclinical data indicate a role for PBI-05204 against glioblastoma multiforme when combined with chemotherapy and radiotherapy. A randomized phase II trial is currently being designed.
Insights
A novel plant extract, PBI-05204, showed some efficacy in metastatic pancreatic cancer patients but did not meet the primary survival endpoint. Further trials are needed to explore its potential in cancer treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic pancreatic ductal adenocarcinoma (mPDA) has a poor prognosis, necessitating novel therapeutic agents.
- PBI-05204, a Nerium oleander extract, contains oleandrin, which exhibits antitumor activity via Akt and mTOR pathway inhibition.
- The extract is being investigated for its potential in treating refractory cancers.
Purpose of the Study:
- To evaluate the efficacy and safety of PBI-05204 in patients with refractory metastatic pancreatic ductal adenocarcinoma (mPDA).
- To determine the overall survival (OS) and progression-free survival (PFS) in patients treated with PBI-05204.
- To assess the overall response rate and safety profile of the novel agent.
Main Methods:
- A Phase II, single-arm, open-label study was conducted.
- Patients with refractory mPDA received daily oral PBI-05204 until disease progression, toxicity, or withdrawal.
- Primary endpoint was OS at 4.5 months; secondary endpoints included PFS and response rate.
Main Results:
- The study included 42 patients, with 38 analyzed; 26.3% survived at 4.5 months, falling short of the 50% hypothesis.
- Median PFS was 56 days, with one objective response (2.6%) lasting 162 days.
- Grade 3 or higher adverse events occurred in 63.2% of patients, most commonly fatigue, vomiting, nausea, decreased appetite, and diarrhea.
Conclusions:
- PBI-05204 did not meet the primary OS endpoint in this study of refractory mPDA.
- The agent was generally well-tolerated, with manageable side effects.
- Further research, including a planned randomized Phase II trial, is warranted to explore PBI-05204's role in cancer therapy, potentially in combination regimens.
