Hilar CholangiocarcinomaPhase 3NCT02082522
Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)
A Phase 3 study testing Photodynamic therapy-Photofrin, Stenting procedure and Chemotherapy regimen in people with Hilar Cholangiocarcinoma, run by Concordia Laboratories Inc. at 31 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hilar Cholangiocarcinoma
- What is being tested?
- Photodynamic therapy-Photofrin, Stenting procedure and Chemotherapy regimen
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 31 sitesin 5 countries
- Study dates
- 12 Nov 2014to 12 Jan 2017
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
31 sites in 5 countries.
31 sites in 5 countries
United States18 sites
University of Colorado Denver
Aurora, Colorado, 80045
SUNY Downstate Medical Center
Brooklyn, New York, 11203
Roswell Park Cancer Institute
Buffalo, New York, 14263
Methodist Dallas Medical Center
Dallas, Texas, 75208
Henry Ford Health System
Detroit, Michigan, 48202
Duke University Medical Center
Durham, North Carolina, 27710
Western Regional Medical Center, Inc.
Goodyear, Arizona, 85338
Oschner Medical Center
Kenner, Louisiana, 70065
University of Southern California Keck School of Medicine
Los Angeles, California, 90033-1026
Weill Cornell Medical College
New York, New York, 10021
Columbia University Medical Center
New York, New York, 10032
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Allegheny Center for Digestive Health - AHN ASRI
Pittsburgh, Pennsylvania, 15212
UC Davis Medical Center
Sacramento, California, 95817
Mayo Clinic Cancer Center
Scottsdale, Arizona, 85259-5499
Virginia Mason Medical Center
Seattle, Washington, 98101
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southwestern Regional Medical Center, Inc.
Tulsa, Oklahoma, 74133
Germany5 sites
Universitätsklinikum Essen (AöR)
Essen, North Rhine-Westphalia, D-45147
Johann-Wolfgang-Goethe Universität Frankfurt
Frankfurt am Main, Hesse, 60590
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Klinikum Ludwigsburg
Ludwigsburg, Baden-Wurttemberg, 71640
Klinikum Mannheim GmbH
Mannheim, Baden-Wurttemberg, 68167
South Korea5 sites
Soonchunhyang University Bucheon Hospital
Bucheon-si, Gyeonggi-do, 420-767
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 463-707
Konkuk University Medical Center
Seoul, Gwangjin-gu, 143-729
Severance Hospital, Yonsei University Health System
Seoul, Seodaemun-gu, 120-752
Seoul National University Hospital
Seoul, 110-744
Canada2 sites
CHUM Hôpital St-Luc
Montreal, Quebec, H2X 3J4
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
About this study
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
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.
Read the 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
- Being tested
- Photodynamic therapy-Photofrin, Stenting procedure, Chemotherapy regimen
- 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
- Medical subject headings
- Klatskin Tumor, Cholangiocarcinoma, Bile Duct Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Photodynamic therapy-PhotofrinDrug
Also called PDT-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.
Stenting procedureProcedure or surgery
Also called Stents placement
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 regimenDrug
Also called Gemcitabine/Cisplatin
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.
| Study group | Role | What they receive |
|---|---|---|
| Photodynamic therapy-Photofrin plus SMC | Experimental | 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. Receives: Drug: Photodynamic therapy-Photofrin; Procedure: Stenting procedure; Drug: Chemotherapy regimen |
| Standard Medical Care (SMC) | Active comparator | 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. Receives: Procedure: Stenting procedure; Drug: Chemotherapy regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 26 months
Secondary outcomes (21)
Time-to-bilirubin Response
From the date of randomization until the date of first documented bilirubin response
Measured: 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)
Measured: Up to 26 months
Time-to-tumor Progression
From the date of first documented response until the date that tumor progression was assessed
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 78 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2014 (estimated)
- Study start12 Nov 2014
- Primary completion12 Jan 2017
- Study completion12 Jan 2017
Why it stopped: Accrual rate remaining too low
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hilar CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Concordia Laboratories Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michel Kahaleh, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02082522
- Sponsor's protocol ID
- PIN-PHO1201
- Status last verified
- Aug 2019
- First submitted
- 6 Mar 2014
- Last updated
- 28 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: The study was prematurely discontinued meaning only descriptive analyses are possible. It is not feasible to share this sort of data.