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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02082522
Recruitment Status : Terminated (Accrual rate remaining too low)
First Posted : March 10, 2014
Results First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Hilar Cholangiocarcinoma Drug: Photodynamic therapy-Photofrin Procedure: Stenting procedure Drug: Chemotherapy regimen Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 12, 2014
Actual Primary Completion Date : January 12, 2017
Actual Study Completion Date : January 12, 2017


Arm Intervention/treatment
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.
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

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.
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Time-to-bilirubin Response [ Time Frame: Up to 30 days ]
    From the date of randomization until the date of first documented bilirubin response

  2. 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)

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02082522


  Show 31 Study Locations
Sponsors and Collaborators
Concordia Laboratories Inc.
Investigators
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Principal Investigator: Michel Kahaleh, MD Weill Medical College of Cornell University

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Responsible Party: Concordia Laboratories Inc.
ClinicalTrials.gov Identifier: NCT02082522     History of Changes
Other Study ID Numbers: PIN-PHO1201
First Posted: March 10, 2014    Key Record Dates
Results First Posted: August 26, 2019
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
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.
Keywords provided by Concordia Laboratories Inc.:
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
Additional relevant MeSH terms:
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Cholangiocarcinoma
Klatskin Tumor
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Dihematoporphyrin Ether
Hematoporphyrin Derivative
Trioxsalen
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Dermatologic Agents
Photosensitizing Agents