Clinical trial NCT02082522: Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hilar Cholangiocarcinoma
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
Lead sponsor: Concordia Laboratories Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-10
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival Time
timeFrame: Up to 26 months
Secondary outcomes:
measure: Time-to-bilirubin Response
timeFrame: Up to 30 days
measure: Best Overall Tumor Response as Measured by the RECIST 1.1 Criteria (Response Evaluation Criteria in Solid Tumors)
timeFrame: Up to 26 months
measure: Time-to-tumor Progression
timeFrame: Up to 26 months
measure: Change From Baseline on Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 7 days
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, up to 4 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 13 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 29 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 41 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 54 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 66 weeks
measure: Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)
timeFrame: Baseline, 78 weeks
measure: 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)
timeFrame: Baseline, 7 days
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, up to 4 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 13 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 16 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 29 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 41 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 54 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 66 weeks
measure: Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30
timeFrame: Baseline, 78 weeks
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Western Regional Medical Center, Inc.
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California Keck School of Medicine
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Kenner
country: United States
facility: Oschner Medical Center
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Tulsa
country: United States
facility: Southwestern Regional Medical Center, Inc.
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Center for Digestive Health - AHN ASRI
state: Pennsylvania
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM Hôpital St-Luc
state: Quebec
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
state: Baden Wuerttemberg
city: Mannheim
country: Germany
facility: Klinikum Mannheim GmbH
state: Baden Wuerttemberg
city: Frankfurt
country: Germany
facility: Johann-Wolfgang-Goethe Universität Frankfurt
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitätsklinikum Essen (AöR)
state: Nordrhein Westfalen
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
state: Gwangjin-gu
city: Bucheon City
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seodaemun-gu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
Study officials:
affiliation: Weill Medical College of Cornell University
name: Michel Kahaleh, MD
role: PRINCIPAL_INVESTIGATOR
References: