PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer

A Multi-Center Randomised Open-Label Phase 2 Study to Assess the Safety, Tolerability and Efficacy of Fimaporfin-Induced Photochemical Internalisation of Gemcitabine Complemented by Gemcitabine/Cisplatin Chemotherapy Versus Gemcitabine/Cisplatin Alone in Patients With Inoperable Cholangiocarcinoma

This study will assess the safety and effectiveness of fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable cholangiocarcinoma (CCA). Participants will be randomly assigned to one of the treatment groups and will receive study treatment for 6 months, followed by assessments every 3 months, as applicable.

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma arising from cells lining the bile ducts. Standard treatment options for CCA include surgery, radiotherapy and chemotherapy, dependent upon if the CCA is intra- or extra-hepatic. Surgical removal of the tumor is the only potential cure, and CCA is very resistant to standard pharmaceutical drug treatment, though chemotherapy has some effect. Current chemotherapy uses cisplatin plus gemcitabine. Photochemical internalisation (PCI) is a novel technology, where photochemical reactions are used to enhance the effect of drugs by increasing their ability cross cell membranes to interact with their intended target. This study will assess the safety and effectiveness of fimaporfin-induced PCI of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable CCA.

NOTE: Participants are no longer being recruited to this study.

Inclusion Criteria:

1. Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements.
2. Histopathologically/cytologically verified adenocarcinoma consistent with cholangiocarcinoma (CCA). Must have biliary lesion causing bile obstruction that requires stenting and is accessible for PCI light treatment (ie, extrahepatic CCA [perihilar or distal] only).
3. CCA must be considered inoperable with respect to radical resection.
4. At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation.
5. If metastatic, metastases must be limited tissues other than bone or the central nervous system.
6. Must have adequate biliary drainage (at least 50% of the liver volume or at least 2 sectors) with no evidence of active uncontrolled infection (patients on antibiotics are eligible).
7. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

1. Patients who have previously received any anti-tumor (either local or systemic) treatment for CCA, except for previous treatment of up to 2 cycles of gemcitabine/cisplatin.
2. Patients with severe visceral disease other than CCA.
3. A history of frequently recurring septic biliary events.
4. Patients with porphyria or hypersensitivity to porphyrins.
5. Patients with a second primary cancer with a disease-free interval of <5 years. A second primary cancer that has been treated with intent to cure may be allowed after consultation with the study Medical Monitor. Adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, in-situ carcinoma of the uterine cervix, or prostate cancer that is controlled by hormone therapy (patients may continue hormone therapy while on study) are allowed.
6. Patients not able to undergo contrast-enhanced CT or MRI.
7. Patients currently participating in any other interventional clinical trial.
8. Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment.
9. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment.
10. Clinically significant and uncontrolled cardiac disease except for extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation.
11. Known allergy or sensitivity to photosensitisers (active substance and/or any of the excipients); or chronic use of other photosensitising therapies; treatment with amiodarone during the last 12 months.
12. Known hypersensitivity to or contraindication to the use of gemcitabine (active substance and/or any of the excipients).
13. Known hypersensitivity to or contraindication to the use of cisplatin (active substance and/or any of the excipients).
14. Patients with ataxia telangiectasia.
15. Upon the Investigator's discretion, evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the planned PCI treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
16. Patients planning to have or who have recently had vaccination with a live vaccine.
17. Patients concurrently receiving treatment with phenytoin.
18. Male patients unwilling to use highly effective contraception or female patients of childbearing potential unwilling to use highly effective form of contraception. Patients must continue the use of contraception during PCI treatment and subsequent chemotherapy for at least 6 months thereafter.
19. Women who are breastfeeding or who have a positive pregnancy test at baseline.
20. Patients with inadequate bone marrow function (absolute neutrophil count <1.5 x 10^9/L; platelet count <100 x 10^9/L; haemoglobin <6 mmol/L [transfusion allowed]).
21. Inadequate liver function despite satisfactory drainage (serum bilirubin persisting at >5 x upper limit of normal for the institution; aspartate aminotransferase or alanine aminotransferase >3.0 x upper limit of normal or >5 x upper limit of normal if liver metastases are present; alkaline phosphatase levels >5.0 x upper limit of normal).
22. Inadequate renal function, as determined by local practice for patients on fractionated platinum-based chemotherapy. Patients with creatinine clearance <45 mL/min (in France: <60 mL/min) must not be included.

Other protocol-defined criteria may apply.