Clinical Summary: 

• Design/Population: The randomized phase 2 TRIPP-FFX trial enrolled patients with locally advanced unresectable pancreatic cancer to receive FOLFIRINOX alone or FOLFIRINOX plus endoscopic ultrasound-guided intratumoral implantation of phosphorus-32 (P-32) microparticles. The primary end point was local disease control at 16 weeks.
• Key Outcomes: The study met its primary end point, demonstrating high rates of local disease control with P-32 implantation. Compared with FOLFIRINOX alone, the combination produced higher objective response rates, greater tumor shrinkage, and numerically longer local progression-free and overall survival, without new safety signals.
• Clinical Relevance: These findings support intratumoral P-32 brachytherapy as a promising locoregional strategy to complement systemic chemotherapy and improve local tumor control in patients with locally advanced pancreatic cancer.

Michele Milella, MD, University of Verona, Verona, Italy, discusses results from the phase 2 TRIPP-FFX trial evaluating endoscopic ultrasound-guided intratumoral phosphorus-32 (P-32) microparticle implantation in combination with FOLFIRINOX for patients with locally advanced unresectable pancreatic cancer.

The study demonstrated that adding P-32 brachytherapy to FOLFIRINOX achieved the prespecified local disease control endpoint while improving tumor response and showing favorable trends in survival outcomes. Dr Milella also highlights the potential role of intratumoral brachytherapy as a novel strategy to consolidate systemic disease control and increase the likelihood of successful surgical resection in selected patients.

Transcript: 

I am Michele Milella, and I'm the director of the medical oncology section at the University of Verona. Together with my colleague and friend Giuseppe Malleo, I coled the group of investigators that conducted the TRIPP-FFX trial using intratumoral implantation of P-32 microparticles together with FOLFIRINOX in locally advanced pancreatic cancer.

Basically, this is a form of brachytherapy that is implanted directly into the tumor and uses phosphorus-32 as a beta emitter. The implant procedure is performed endoscopically under endoscopic ultrasound guidance. In this particular trial, this approach was tested in combination with systemic chemotherapy using FOLFIRINOX for patients with locally advanced unresectable pancreatic cancer.

Because locally advanced unresectable pancreatic cancer is a relatively limited disease setting but also a highly heterogeneous one, we elected to randomize the study against FOLFIRINOX alone, which is an accepted standard of care. However, the randomization was not meant for a direct comparison between FOLFIRINOX and FOLFIRINOX plus P-32 microparticle implantation. Rather, it served as an internal control and calibration arm to make sure that the patient population we were targeting was clinically meaningful and representative of the locally advanced pancreatic cancer setting.

A total of 88 patients were randomized to receive either FOLFIRINOX alone or FOLFIRINOX plus P-32 microparticle implantation. In the experimental arm, the P-32 microparticles were implanted 4 weeks after the beginning of chemotherapy, and then chemotherapy was resumed as planned. Forty-five patients were randomized to the experimental arm, and 43 were randomized to FOLFIRINOX alone. This constituted the intention-to-treat population. We also analyzed the per-protocol population, which consisted of the 40 patients who actually received the implant.

Of the 5 patients who did not receive the implant, 1 did not because of a technical problem, while the other 4 underwent CT scans documenting systemic progression before implantation and therefore were not implanted. In addition, 2 patients assigned to the FOLFIRINOX arm never actually started FOLFIRINOX. The safety population included all patients who received at least one cycle of FOLFIRINOX.

As for the results, the primary end point of the study was local disease control at 16 weeks. The lower boundary of the confidence interval that we wanted to exclude was a local disease control rate of 55%, while the upper boundary was 75%. 

In the experimental arm, local disease control at 16 weeks reached 82.2% in the intention-to-treat population and 85% in the per-protocol population. Similar results were also obtained in the FOLFIRINOX-alone arm, with approximately 85% local disease control. 

However, the overall response rate was higher in the FOLFIRINOX plus P-32 microparticle arm, ranging between 55% and 60%, depending on whether the intention-to-treat or per-protocol population was considered, compared with approximately 36% to 37% in the FOLFIRINOX-alone arm. The amount of tumor volume shrinkage was also greater, with a median reduction of 72% in the P-32 plus FOLFIRINOX arm compared with 56% in the FOLFIRINOX-alone arm. 

With regard to the time-based end points, local progression-free survival, progression-free survival, and overall survival all numerically favored the FOLFIRINOX plus P-32 microparticle arm. Median overall survival reached approximately 18 months in the intention-to-treat population and 21 months in the per-protocol population in the experimental arm. No new safety signals were identified.

I should remind you that implantation of P-32 microparticles had already been tested previously in combination with gemcitabine-based chemotherapy backbones. 

In conclusion, this study successfully met its primary endpoint and demonstrated manageable toxicity together with a local disease control rate exceeding 80% at 16 weeks. All of the secondary end points were generally in line with the best results we can obtain using combined systemic and locoregional treatment in locally advanced pancreatic cancer. 

In particular, overall response rate, local progression-free survival, progression-free survival, and overall survival all numerically favored the P-32 microparticle plus FOLFIRINOX arm. Twelve percent of patients underwent surgical resection in both the control and experimental arms. However, the R0 resection rate reached 60% in the experimental arm compared with 33% in the control arm.

We believe that the addition of intratumoral P-32 microparticle implantation could represent a viable therapeutic strategy in locally advanced pancreatic cancer by consolidating the systemic disease control achieved with chemotherapy and providing a flexible and innovative approach to improving local disease control in these patients.

Source: 

TRIPP-FFX: Results of an open-label, multi-centre, randomized study of TaRgeted Intratumoural Placement of Phosphorous-32 microparticles in addition to FOLFIRINOX versus FOLFIRINOX alone in patients with unresectable locally advanced pancreatic cancer (uLAPC). Presented at ESMO Gastrointestinal Cancers Congress. July 1-4, 2026. Munich, Germany. LBA4.