PCI Biotech has chosen bile duct cancer (cholangiocarcinoma) as the next indication for the use of its PCI (photochemical internalisation) localised cancer therapy. In this indication PCI's photosensitiser, Amphinex, will be used in combination with the generic cytotoxic agent, gemcitabine. The aim is to start the clinical proof-of-concept study by the end of the first half of 2013.
Currently, surgery is the only curative option for bule duct cancer patients, despite the majority of the patients being inoperable at this stage. Inoperable patients are treated with stenting to keep the bile duct open and with chemotherapy. The combination of gemcitabine and cisplatin has shown promising results and has become standard treatment in some regions, but there is still a need for better treatments to increase overall survival and quality of life.
Improved local methods to slow tumour progression and keep the bile duct open are important to extend life span and quality. Bile duct cancer is characterised by a remarkable resistance to common chemotherapy, and new drug classes or alternative methods are needed. The most studied and used drug is gemcitabine, which is one of the identified drugs that are significantly enhanced by PCI in preclinical studies. Light access is provided through the endoscopic methods that are routinely used in the treatment of this disease.
The proof-of-concept study is planned to be an open-label, multicentre Phase I/II trial at up to 45 patients to assess the safety and efficacy of Amphinex-induced PCI of gemcitabine, followed by systemic cisplatin/gemcitabine in patients with inoperable bile duct cancer. The study will consist of a dose-escalation/Phase I part to assess the tolerance of local bile duct treatment and a randomised double-arm Phase II part. In Phase II, patients will be randomised to either a control arm (stenting alone followed by gemcitabine/cisplatin chemotherapy) or the PCI arm (stenting followed by Amphinex-induced PCI treatment of gemcitabine followed by gemcitabine/cisplatin chemotherapy). The randomisation ratio for this study is 2.5:1 in favour of the PCI arm. The Phase I primary objective will be to determine a tolerable dose for local bile duct treatment with Amphinex-induced PCI of gemcitabine, while the Phase II primary objective will be to assess efficacy in terms of progression-free survival.
Patient enrolment is expected to be completed by 2014. Inclusion of patients is estimated to take approximately six months in Phase I and approximately ten months in Phase II. Estimated costs for the study is approximately NKr 7 million for Phase I and approximately NKr 11 million for Phase II.
PCI has already completed inclusion of patients in the Phase I/II extension study of Amphinex in combination with the cytotoxic agent bleomycin. The objective of the study is to investigate doses below the levels used in the Phase I/II study that was completed in 2011. The extension study is performed at University College Hospital (UCH) in London, UK. Three patients were treated in the extension study with an Amphinex dose of 0.125mg/kg and it has been decided that there is no need for further reduction of the Amphinex dose. Results from the three patients supports the previously selected dose of 0.25mg/kg for the Phase II study of Amphinex in combination with bleomycin in the treatment of head and neck cancer patients. Inclusion of patients in the Phase II study started earlier in May.