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

NCT ID: NCT02082522

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-12
• Study Completion Date: 2017-01-12

Brief 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.

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.

Conditions

Hilar Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Photodynamic therapy-Photofrin

Intervention Type: DRUG

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.

Stenting procedure

Intervention Type: 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.

Chemotherapy regimen

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Stenting procedure

Intervention Type: 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.

Chemotherapy regimen

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Other Intervention Names

PDT-Photofrin; Stents placement; Gemcitabine/Cisplatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Concordia Laboratories Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel Kahaleh, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Western Regional Medical Center, Inc.

Goodyear, Arizona, United States

Mayo Clinic Cancer Center

Scottsdale, Arizona, United States

University of Southern California Keck School of Medicine

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Oschner Medical Center

Kenner, Louisiana, United States

Henry Ford Health System

Detroit, Michigan, United States

SUNY Downstate Medical Center

Brooklyn, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Weill Cornell Medical College

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Southwestern Regional Medical Center, Inc.

Tulsa, Oklahoma, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Allegheny Center for Digestive Health - AHN ASRI

Pittsburgh, Pennsylvania, United States

Methodist Dallas Medical Center

Dallas, Texas, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

St. Michael's Hospital

Toronto, Ontario, Canada

CHUM Hôpital St-Luc

Montreal, Quebec, Canada

Klinikum Ludwigsburg

Ludwigsburg, Baden-Wurttemberg, Germany

Klinikum Mannheim GmbH

Mannheim, Baden-Wurttemberg, Germany

Johann-Wolfgang-Goethe Universität Frankfurt

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Essen (AöR)

Essen, North Rhine-Westphalia, Germany

Konkuk University Medical Center

Seoul, Gwangjin-gu, South Korea

Soonchunhyang University Bucheon Hospital

Bucheon-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Severance Hospital, Yonsei University Health System

Seoul, Seodaemun-gu, South Korea

Seoul National University Hospital

Seoul, , South Korea

UniversitätsSpital Zürich

Zurich, , Switzerland

Countries

United States; Canada; Germany; South Korea; Switzerland

Other Identifiers

PIN-PHO1201

Identifier Type: -

Identifier Source: org_study_id