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

Hilar Cholangiocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02082522
• Other study ID #: PIN-PHO1201
• Status: Terminated
• Phase: Phase 3
• Start date: November 12, 2014
• Est. completion date: January 12, 2017

Study information

• Verified date: August 2019
• Source: Concordia Laboratories Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: January 12, 2017
• Est. primary completion date: January 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Hilar Cholangiocarcinoma
• Klatskin Tumor

Intervention

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.

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.

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.

Locations

Country	Name	City	State
Canada	CHUM Hôpital St-Luc	Montreal	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Germany	Universitätsklinikum Essen (AöR)	Essen	Nordrhein Westfalen
Germany	Johann-Wolfgang-Goethe Universität Frankfurt	Frankfurt	Hessen
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Klinikum Ludwigsburg	Ludwigsburg	Baden Wuerttemberg
Germany	Klinikum Mannheim GmbH	Mannheim	Baden Wuerttemberg
Korea, Republic of	Soonchunhyang University Bucheon Hospital	Bucheon City	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Konkuk University Medical Center	Seoul	Gwangjin-gu
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seodaemun-gu
Switzerland	UniversitätsSpital Zürich	Zürich
United States	University of Colorado Denver	Aurora	Colorado
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Western Regional Medical Center, Inc.	Goodyear	Arizona
United States	Oschner Medical Center	Kenner	Louisiana
United States	University of Southern California Keck School of Medicine	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Allegheny Center for Digestive Health - AHN ASRI	Pittsburgh	Pennsylvania
United States	UC Davis Medical Center	Sacramento	California
United States	Mayo Clinic Cancer Center	Scottsdale	Arizona
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Southwestern Regional Medical Center, Inc.	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Concordia Laboratories Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Korea, Republic of,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time-to-bilirubin Response	From the date of randomization until the date of first documented bilirubin response	Up to 30 days
Secondary	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
Secondary	Time-to-tumor Progression	From the date of first documented response until the date that tumor progression was assessed	Up to 26 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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