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

Phase 3

Terminated

• Conditions: Hilar Cholangiocarcinoma
• Interventions: Drug: Photodynamic therapy-Photofrin; Procedure: Stenting procedure; Drug: Chemotherapy regimen

• Registration Number: NCT02082522
• Lead Sponsor: Concordia Laboratories Inc.

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.

Study Timeline

• Study First Submitted: 2014-03-06
• Study First Submitted QC: 2014-03-07
• Study First Posted: 2014-03-10
• Study Start: 2014-11-12
• Primary Completion: 2017-01-12
• Study Completion: 2017-01-12
• Results First Submitted: 2018-12-31
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-14
• Last Update Submitted: 2019-08-14
• Results First Posted: 2019-08-28
• Last Update Posted: 2019-08-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 28

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Photodynamic therapy-Photofrin plus SMC	Photodynamic therapy-Photofrin	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.
Photodynamic therapy-Photofrin plus SMC	Stenting procedure	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.
Photodynamic therapy-Photofrin plus SMC	Chemotherapy regimen	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.
Standard Medical Care (SMC)	Stenting procedure	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.
Standard Medical Care (SMC)	Chemotherapy regimen	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival Time	Up to 26 months	Time from the date of randomization until the date of death or the last date the subject was known to be alive

Secondary Outcome Measures

Name	Time	Method
Time-to-bilirubin Response	Up to 30 days	From the date of randomization until the date of first documented bilirubin response
Best Overall Tumor Response as Measured by the RECIST 1.1 Criteria (Response Evaluation Criteria in Solid Tumors)	Up to 26 months	From the start of the treatment until disease progression or recurrence the RECIST 1.1 criteria are applied (Response Evaluation Criteria in Solid Tumors)
Time-to-tumor Progression	Up to 26 months	From the date of first documented response until the date that tumor progression was assessed
Change From Baseline on Karnofsky Performance Scale (KPS)	Baseline, 7 days	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.
Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)	Baseline, 78 weeks	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.
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)	Baseline, 7 days	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.
Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30	Baseline, 78 weeks	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.

Trial Locations

Locations (31)

CHUM Hôpital St-Luc; 🇨🇦 Montreal, Quebec, Canada

University of Southern California Keck School of Medicine; 🇺🇸 Los Angeles, California, United States

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

Mayo Clinic Cancer Center; 🇺🇸 Scottsdale, Arizona, United States

Western Regional Medical Center, Inc.; 🇺🇸 Goodyear, Arizona, United States

Soonchunhyang University Bucheon Hospital; 🇰🇷 Bucheon City, Gyeonggi-do, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Johann-Wolfgang-Goethe Universität Frankfurt; 🇩🇪 Frankfurt, Hessen, Germany

Duke University Medical Center; 🇺🇸 Durham, North Carolina, 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

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Methodist Dallas Medical Center; 🇺🇸 Dallas, Texas, United States

Southwestern Regional Medical Center, Inc.; 🇺🇸 Tulsa, Oklahoma, United States

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Allegheny Center for Digestive Health - AHN ASRI; 🇺🇸 Pittsburgh, Pennsylvania, United States

Providence Sacred Heart Medical Center and Children's Hospital; 🇺🇸 Spokane, Washington, United States

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Niedersachsen, Germany

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Seodaemun-gu, Korea, Republic of

Klinikum Ludwigsburg; 🇩🇪 Ludwigsburg, Baden Wuerttemberg, Germany

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

UniversitätsSpital Zürich; 🇨🇭 Zürich, Switzerland

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

Universitätsklinikum Essen (AöR); 🇩🇪 Essen, Nordrhein Westfalen, Germany

Klinikum Mannheim GmbH; 🇩🇪 Mannheim, Baden Wuerttemberg, Germany

Konkuk University Medical Center; 🇰🇷 Seoul, Gwangjin-gu, Korea, Republic of

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States