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

NCT02082522 | Terminated Phase 3 Results DMC

• 1 other identifier: PIN-PHO1201
• Study Type: interventional
• Target: 28
• Locations: 5 countries
• Sites: 31

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• Time-to-bilirubin Response

  Up to 30 days

• Best Overall Tumor Response as Measured by the RECIST 1.1 Criteria (Response Evaluation Criteria in Solid Tumors)

  Up to 26 months

• Time-to-tumor Progression

  Up to 26 months

• Change From Baseline on Karnofsky Performance Scale (KPS)

  Baseline, 7 days

• Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)

  Baseline, up to 4 weeks

Study Arms (2)

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.

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.

Procedure: Stenting procedure; Drug: Chemotherapy regimen

Interventions

Photodynamic therapy-Photofrin DRUG

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.

Also known as: PDT-Photofrin

Photodynamic therapy-Photofrin plus SMC

Stenting procedure 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.

Also known as: Stents placement

Photodynamic therapy-Photofrin plus SMC; Standard Medical Care (SMC)

Chemotherapy regimen DRUG

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.

Also known as: Gemcitabine/Cisplatin

Photodynamic therapy-Photofrin plus SMC; Standard Medical Care (SMC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Concordia Laboratories Inc.: lead

Study Sites (31)

Western Regional Medical Center, Inc.

Goodyear, Arizona, 85338, United States

Location

Mayo Clinic Cancer Center

Scottsdale, Arizona, 85259-5499, United States

Location

University of Southern California Keck School of Medicine

Los Angeles, California, 90033-1026, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Oschner Medical Center

Kenner, Louisiana, 70065, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Southwestern Regional Medical Center, Inc.

Tulsa, Oklahoma, 74133, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny Center for Digestive Health - AHN ASRI

Pittsburgh, Pennsylvania, 15212, United States

Location

Methodist Dallas Medical Center

Dallas, Texas, 75208, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

CHUM Hôpital St-Luc

Montreal, Quebec, H2X 3J4, Canada

Location

Klinikum Ludwigsburg

Ludwigsburg, Baden-Wurttemberg, 71640, Germany

Location

Klinikum Mannheim GmbH

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Johann-Wolfgang-Goethe Universität Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitätsklinikum Essen (AöR)

Essen, North Rhine-Westphalia, D-45147, Germany

Location

Konkuk University Medical Center

Seoul, Gwangjin-gu, 143-729, South Korea

Location

Soonchunhyang University Bucheon Hospital

Bucheon-si, Gyeonggi-do, 420-767, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, Seodaemun-gu, 120-752, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Klatskin Tumor; Cholangiocarcinoma; Bile Duct Neoplasms

Interventions

Drug Therapy; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

This study was prematurely terminated due to low accrual. Consequently, there was insufficient data to allow statistical analysis. Only descriptive statistics are presented for the primary endpoint, overall survival time.

Results Point of Contact

• Title: Dr. Michelle Depot
• Organization: At the request of Concordia Laboratories Inc.

michelle.depot@advanzpharma.com

Study Officials

• Michel Kahaleh, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: November 12, 2014
• Primary Completion: January 12, 2017
• Study Completion: January 12, 2017
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5); CH (1); DE (5); CA (2); US (18)