Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)

Multicenter, Open-label, Randomized, Controlled Phase III Clinical Study of the Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium for Injection as Treatment for Unresectable Advanced Perihilar Cholangiocarcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Hilar Cholangiocarcinoma
• Intervention / Treatment: Drug: Photodynamic therapy-Photofrin; Procedure: Stenting procedure; Drug: Chemotherapy regimen

Detailed Description

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.

Cholangiocarcinoma (CCA) is defined as primary malignant tumors of the bile ducts. The exact etiology remains unknown. These cancerous tumors block the bile flow and can be intrahepatic (IH) or extrahepatic (EH). The distinction between IH- and EH-CCA has become increasingly important, as the epidemiological features (i.e., incidence and risk factors), the biologic and pathologic characteristics and the clinical course are largely different. Unfortunately, most subjects are found to have metastases or unresectable disease at the time of diagnosis. Median survival for subjects with unresectable perihilar-CCA varies between five and eight months. The one-year survival is 50%, with 20% surviving at two years and 10% at three years. Unresected CCA is a rapidly fatal process with cholangitis being a significant cause of morbidity and mortality in these subjects.

This study was designed to confirm the efficacy of PHOPDT + standard medical care (SMC) defined as stents plus gemcitabine/cisplatin chemotherapy regimen on the overall survival of subjects with unresectable cholestasis perihilar Bismuth type III or IV - tumor TNM stage III or IVa CCA.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • CHUM Hopital St-Luc
• Germany
  • Baden Wuerttemberg
    • Ludwigsburg, Baden Wuerttemberg, Germany, 71640
      • Klinikum Ludwigsburg
    • Mannheim, Baden Wuerttemberg, Germany, 68167
      • Klinikum Mannheim GmbH
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Johann-Wolfgang-Goethe Universität Frankfurt
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
  • Nordrhein Westfalen
    • Essen, Nordrhein Westfalen, Germany, D-45147
      • Universitatsklinikum Essen (Aor)
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Gwangjin-gu
    • Seoul, Gwangjin-gu, Korea, Republic of, 143-729
      • Konkuk University Medical Center
  • Gyeonggi-do
    • Bucheon City, Gyeonggi-do, Korea, Republic of, 420-767
      • Soonchunhyang University Bucheon Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
  • Seodaemun-gu
    • Seoul, Seodaemun-gu, Korea, Republic of, 120-752
      • Severance Hospital, Yonsei University Health System
• Switzerland
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center, Inc.
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Cancer Center
  • California
    • Los Angeles, California, United States, 90033-1026
      • University of Southern California Keck School of Medicine
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Louisiana
    • Kenner, Louisiana, United States, 70065
      • Oschner Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY downstate Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Southwestern Regional Medical Center, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Center for Digestive Health - AHN ASRI
  • Texas
    • Dallas, Texas, United States, 75208
      • Methodist Dallas Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Photodynamic therapy-Photofrin plus SMC; Photodynamic therapy (PDT) involves the i.v. injection of Photofrin followed by the illumination of the tumor using a fiber optic device. 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. Standard Medical Care (SMC) is defined as stenting procedure plus chemotherapy regimen.	Drug: Photodynamic therapy-Photofrin; 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.; Other Names: PDT-Photofrin; Procedure: Stenting procedure; 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.; Other Names: Stents placement; Drug: Chemotherapy regimen; 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.; Other Names: Gemcitabine/Cisplatin
Active Comparator: Standard Medical Care (SMC); Standard Medical Care (SMC) is defined as stenting procedure plus chemotherapy regimen. The chemotherapy 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.	Procedure: Stenting procedure; 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.; Other Names: Stents placement; Drug: Chemotherapy regimen; 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.; Other Names: Gemcitabine/Cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Time	Time from the date of randomization until the date of death or the last date the subject was known to be alive	Up to 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-bilirubin Response	From the date of randomization until the date of first documented bilirubin response	Up to 30 days
Best Overall Tumor Response as Measured by the RECIST 1.1 Criteria (Response Evaluation Criteria in Solid Tumors)	From the start of the treatment until disease progression or recurrence the RECIST 1.1 criteria are applied (Response Evaluation Criteria in Solid Tumors)	Up to 26 months
Time-to-tumor Progression	From the date of first documented response until the date that tumor progression was assessed	Up to 26 months
Change From Baseline on Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.	Baseline, 7 days
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale (KPS) scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. A score of 100% means there are no complaints and no evidence of disease. A score of 80% means there is normal activity with effort and some signs or symptoms of disease. A score of 0% means death.	Baseline, up to 4 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale (KPS) scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. A score of 100% means there are no complaints and no evidence of disease. A score of 80% means there is normal activity with effort and some signs or symptoms of disease. A score of 0% means death.	Baseline, 13 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale (KPS) scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. A score of 100% means there are no complaints and no evidence of disease. A score of 80% means there is normal activity with effort and some signs or symptoms of disease. A score of 0% means death.	Baseline, 16 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.	Baseline, 29 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.	Baseline, 41 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.	Baseline, 54 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.	Baseline, 66 weeks
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.	Baseline, 78 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 7 days
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, up to 4 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 13 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 16 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 29 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 41 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 54 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 66 weeks
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.	Baseline, 78 weeks

Collaborators and Investigators

• Sponsor: Concordia Laboratories Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2014
• Primary Completion (Actual): January 12, 2017
• Study Completion (Actual): January 12, 2017

Study Registration Dates

• First Submitted: March 6, 2014
• First Submitted That Met QC Criteria: March 7, 2014
• First Posted (Estimate): March 10, 2014

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 14, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Gemcitabine; Stents; Cisplatin; Chemotherapy; Cholangiocarcinoma; CCA; Photodynamic therapy; PDT; Bile duct cancer; Unresectable perihilar cholangiocarcinoma; Klatskin tumor; Porfimer sodium; Photofrin; Bile duct tumor; Bile duct adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Klatskin Tumor; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Photosensitizing Agents; Dermatologic Agents; Gemcitabine; Cisplatin; Dihematoporphyrin Ether; Trioxsalen; Hematoporphyrin Derivative
• Other Study ID Numbers: PIN-PHO1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The study was prematurely discontinued meaning only descriptive analyses are possible. It is not feasible to share this sort of data.