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

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ClinicalTrials.gov Identifier: NCT02082522
Recruitment Status : Terminated (Accrual rate remaining too low)
First Posted : March 10, 2014
Results First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Concordia Laboratories Inc.

Tracking Information
First Submitted Date  ICMJE March 6, 2014
First Posted Date  ICMJE March 10, 2014
Results First Submitted Date  ICMJE December 31, 2018
Results First Posted Date  ICMJE August 28, 2019
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE November 12, 2014
Actual Primary Completion Date January 12, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
Overall Survival Time [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: March 7, 2014)
Overall survival [ Time Frame: Up to 4.5 years ]
From the date of randomization until the date of death or the last date the subject was known to be alive
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
  • Time-to-bilirubin Response [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline, up to 4 weeks ]
    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.
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 13 weeks ]
    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.
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 16 weeks ]
    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.
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 29 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 Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 41 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 Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 54 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 Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 66 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 Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline, up to 4 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 13 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 16 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 29 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 41 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 54 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 66 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.
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2014)
  • Time-to-bilirubin Response [ Time Frame: Up 30 days ]
    From the date of randomization until the date of first documented bilirubin response
  • Best overall tumor response [ Time Frame: Up to 4.5 years ]
    From the start of the treatment until disease progression or recurrence
  • Time-to-tumor Progression [ Time Frame: Up to 4.5 years ]
    From the date of first documented response until the date that tumor progression was assessed
  • Change from baseline in performance status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 7 days ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, up to 4 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 13 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 16 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 29 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 41 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 54 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 66 weeks ]
    The KPS scores range from 0% to 100%
  • Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS) [ Time Frame: Baseline, 78 weeks ]
    The KPS scores range from 0% to 100%
  • 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) [ Time Frame: Baseline, 7 days ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, up to 4 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 13 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 16 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 29 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 41 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 54 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 66 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
  • Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30 [ Time Frame: Baseline, 78 weeks ]
    Final scores for multi-item scales and single-item measures will range from 0 to 100
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hilar Cholangiocarcinoma
Intervention  ICMJE
  • 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.
    Other Name: PDT-Photofrin
  • 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.
    Other Name: Stents placement
  • 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.
    Other Name: Gemcitabine/Cisplatin
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Photodynamic therapy-Photofrin
    • Procedure: Stenting procedure
    • Drug: Chemotherapy regimen
  • Active Comparator: 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.
    Interventions:
    • Procedure: Stenting procedure
    • Drug: Chemotherapy regimen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 19, 2016)
28
Original Estimated Enrollment  ICMJE
 (submitted: March 7, 2014)
200
Actual Study Completion Date  ICMJE January 12, 2017
Actual Primary Completion Date January 12, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Korea, Republic of,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02082522
Other Study ID Numbers  ICMJE PIN-PHO1201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: The study was prematurely discontinued meaning only descriptive analyses are possible. It is not feasible to share this sort of data.
Responsible Party Concordia Laboratories Inc.
Study Sponsor  ICMJE Concordia Laboratories Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michel Kahaleh, MD Weill Medical College of Cornell University
PRS Account Concordia Laboratories Inc.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP