Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)
Condition: Hilar Cholangiocarcinoma
MeSH terms: Cholangiocarcinoma; Klatskin Tumor
Intervention: Photodynamic therapy-Photofrin; Stenting procedure; Chemotherapy regimen
Intervention description: Photodynamic therapy (PDT) involves the i.v. injection of Photofrin (2 mg/kg) followed by the illumination of the tumor using a fiber optic device during an endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). Two days after the injection, a laser light (180 J/cm(2)) will be applied to the tumor. A second light application will be given 96-120 hours after Photofrin injection if PDT could not initially be performed on all sides of the tumor. Post illumination, all patients will undergo stenting as part of standard medical care procedure. Up to 3 additional courses of PDT using a light dose of 120 J/cm(2) may be given at 3-month intervals.; As per standard medical procedures, stenting procedure consists in the placement of stents above the main tumors of the right and left hepatic bile ducts via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) when the ERCP approach has been unsuccessful.; The regimen will comprise gemcitabine (1 000 mg/m(2)) followed by cisplatin (25 mg/m(2)), each administered on days 1 and 8 every 3 weeks (21 day-cycle) for four cycles. An additional 12 weeks of the same chemotherapy regimen may be administered if there is no disease progression or intolerable toxicity.
Intervention MeSH terms: Cisplatin; Gemcitabine; Dihematoporphyrin Ether; Hematoporphyrin Derivative; Trioxsalen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cholangiocarcinoma; Unresectable perihilar cholangiocarcinoma; Klatskin tumor; Photodynamic therapy; Porfimer sodium; Photofrin; Gemcitabine; Cisplatin; Stents; CCA; PDT; Bile duct cancer; Bile duct tumor; Bile duct adenocarcinoma; Chemotherapy

Summary:

      Photodynamic therapy (PDT) is a combination of a drug, porfimer sodium (Photofrin), which is
      activated by a light from a laser that emits no heat. This technique works to allow the
      medical doctor to specifically target and destroy abnormal or cancer cells while limiting
      damage to surrounding healthy tissue. The activation of the drug is done by lighting the
      abnormal areas using a fiber optic device (very fine fiber like a fishing line that permits
      light transmission) inserted into a flexible tube with a light called cholangioscope for the
      bile duct. The light will activate the porfimer sodium concentrated in the abnormal tissue,
      leading to its destruction.

      This research study will evaluate the efficacy and safety of PDT with porfimer sodium
      administered with Standard Medical Care (SMC) compared to SMC alone on the overall survival
      time of patients with non-operable advanced cholangiocarcinoma, a rare cancer of the bile
      ducts. It will involve 200 patients across North America and Europe. Other countries may
      participate if needed. Participation will last at least 18 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females aged 18 or older

          -  Diagnosed with radiologically and biopsy or cytology confirmed inoperable perihilar
             cholangiocarcinoma Bismuth Tumor Stage III/IV

          -  Non-menopausal or non-sterile female subjects of childbearing potential must have a
             negative serum beta-HCG and use a medically acceptable form of birth control

          -  Able to sign an informed consent

        Exclusion Criteria:

          -  Diagnostic of cholangiocarcinoma made more than 45 days prior to randomization

          -  Cholangiocarcinoma with extra-hepatic metastasis or concurrent non-solid malignancy

          -  Presence or history of other neoplasms (treated during the last five years prior to
             study entry) other than carcinoma in situ of the cervix or basal carcinoma of the skin

          -  Previously received photodynamic therapy for cholangiocarcinoma

          -  Previously undergone surgical resection of the cholangiocarcinoma

          -  Previously undergone chemotherapy, brachytherapy, or radiotherapy prior to entering
             the study

          -  Previously undergone metal stent insertion

          -  Porphyria or hypersensitivity to porphyrins (constituents of porfimer sodium),
             gemcitabine, cisplatin or other platinum-containing compounds

          -  Presence of infection other than the infection of the bile duct (cholangitis)

          -  Acute or chronic medical or psychological illnesses that prevent endoscopy procedures

          -  Abnormal blood test results

          -  Severe impairment of your kidney or liver function

          -  Decompensated cirrhosis

          -  Pregnant or intend to become pregnant, breastfeeding or intend to breast-feed during
             this study

          -  Participated in another drug study within 90 days before this one

          -  Unable or unwilling to complete the follow-up evaluations required for the study