PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer
Condition: Cholangiocarcinoma
MeSH terms: Cholangiocarcinoma
Intervention: Fimaporfin and Gemcitabine; Gemcitabine/Cisplatin chemotherapy
Intervention description: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given.; Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase II; Safety; Tolerability; Efficacy; Amphinex-induced Photochemical Internalisation; PCI; Amphinex; Gemcitabine; Cisplatin; Inoperable; CCA; Cholangiocarcinoma; Bile duct cancer; Photodynamic therapy; Extrahepatic; Perihilar; Distal; Fimaporfin; Pivotal; RELEASE; PDT; FimaChem; Klatskin; First line treatment; Standard of care; SOC; Chemotherapy; Local treatment

Summary:

      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.
    

Eligibility criteria:

        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.