Cholangiocarcinoma is a rare cancer with a poor survival and an approximate response rate of 26% and a median PFS/OS of 8.0 and 11.7months respectively with current standard treatment (gemcitabine/cisplatin). Photochemical Internalisation (PCI) is a novel technology that utilizes wave-length specific light (652nm) and a photosensitizer (TPCS2a ; Amphinex®) to enhance the local therapeutic effect of a variety of molecules, including gemcitabine.
This was a Phase I, dose escalation, multicenter trial of a single PCI induction of gemcitabine (1000 mg/m2) in 16 patients with inoperable perihilar cholangiocarcinoma (CCA). Following the procedure, patients received standard therapy with gem/cis for up to 8 cycles. Patients were on-study for 6 months, and are currently followed for survival. Adverse events, including biliary complications, and tumor effects were characterized.
A total of 16 patients were treated in four different dose cohorts. 11 patients completed the 8 cycles of combination therapy; 5 patients were early withdrawals. PCI of gemcitabine was well tolerated with no Dose Limiting Toxicities, and with a general safety profile characteristic of the patient population included. At 6 months, in the two highest dose cohorts independent reading showed that 7 out of 8 patients had radiologically evaluable tumours. Of these, 2 were complete and 2 partial responses, with one stable disease. In 17/19 target lesions before treatment, a > 20% reduction in tumour size was seen, with 12 lesions undetectable at 6 months. Median OS ended at 14.4 months. As of March 2018, 4 of the 16 patients are alive 24.3 to 38.8 months after treatment (overall study average 17.4 months).
In this dose escalation trial of PCI of gemcitabine in perihilar CCA patients, a safe and tolerable dose of light and Amphinex® was established. The overall safety profile and promising results, including a proportion of patients with highly durable objective tumor response, are encouraging. A larger, controlled and randomized study is underway.
Clinical trial identification
Legal entity responsible for the study
PCI Biotech AS.
PCI Biotech AS.
A. Högset, L. Finnesand, H. Olivecrona: Employee: PCI Biotech AS. All other authors have declared no conflicts of interest.