PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer
- Conditions
- Cholangiocarcinoma
- Interventions
- Drug: Gemcitabine/Cisplatin chemotherapy
- Registration Number
- NCT04099888
- Lead Sponsor
- PCI Biotech AS
- Brief Summary
This study will assess the safety and effectiveness of fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable cholangiocarcinoma (CCA). Participants will be randomly assigned to one of the treatment groups and will receive study treatment for 6 months, followed by assessments every 3 months, as applicable.
- Detailed Description
Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma arising from cells lining the bile ducts. Standard treatment options for CCA include surgery, radiotherapy and chemotherapy, dependent upon if the CCA is intra- or extra-hepatic. Surgical removal of the tumor is the only potential cure, and CCA is very resistant to standard pharmaceutical drug treatment, though chemotherapy has some effect. Current chemotherapy uses cisplatin plus gemcitabine. Photochemical internalisation (PCI) is a novel technology, where photochemical reactions are used to enhance the effect of drugs by increasing their ability cross cell membranes to interact with their intended target. This study will assess the safety and effectiveness of fimaporfin-induced PCI of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable CCA.
NOTE: Participants are no longer being recruited to this study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 41
- Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements.
- Histopathologically/cytologically verified adenocarcinoma consistent with cholangiocarcinoma (CCA). Must have biliary lesion causing bile obstruction that requires stenting and is accessible for PCI light treatment (ie, extrahepatic CCA [perihilar or distal] only).
- CCA must be considered inoperable with respect to radical resection.
- At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation.
- If metastatic, metastases must be limited tissues other than bone or the central nervous system.
- Must have adequate biliary drainage (at least 50% of the liver volume or at least 2 sectors) with no evidence of active uncontrolled infection (patients on antibiotics are eligible).
- Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Estimated life expectancy of at least 12 weeks.
- Patients who have previously received any anti-tumor (either local or systemic) treatment for CCA, except for previous treatment of up to 2 cycles of gemcitabine/cisplatin.
- Patients with severe visceral disease other than CCA.
- A history of frequently recurring septic biliary events.
- Patients with porphyria or hypersensitivity to porphyrins.
- Patients with a second primary cancer with a disease-free interval of <5 years. A second primary cancer that has been treated with intent to cure may be allowed after consultation with the study Medical Monitor. Adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, in-situ carcinoma of the uterine cervix, or prostate cancer that is controlled by hormone therapy (patients may continue hormone therapy while on study) are allowed.
- Patients not able to undergo contrast-enhanced CT or MRI.
- Patients currently participating in any other interventional clinical trial.
- Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment.
- Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment.
- Clinically significant and uncontrolled cardiac disease except for extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation.
- Known allergy or sensitivity to photosensitisers (active substance and/or any of the excipients); or chronic use of other photosensitising therapies; treatment with amiodarone during the last 12 months.
- Known hypersensitivity to or contraindication to the use of gemcitabine (active substance and/or any of the excipients).
- Known hypersensitivity to or contraindication to the use of cisplatin (active substance and/or any of the excipients).
- Patients with ataxia telangiectasia.
- Upon the Investigator's discretion, evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the planned PCI treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
- Patients planning to have or who have recently had vaccination with a live vaccine.
- Patients concurrently receiving treatment with phenytoin.
- Male patients unwilling to use highly effective contraception or female patients of childbearing potential unwilling to use highly effective form of contraception. Patients must continue the use of contraception during PCI treatment and subsequent chemotherapy for at least 6 months thereafter.
- Women who are breastfeeding or who have a positive pregnancy test at baseline.
- Patients with inadequate bone marrow function (absolute neutrophil count <1.5 x 10^9/L; platelet count <100 x 10^9/L; haemoglobin <6 mmol/L [transfusion allowed]).
- Inadequate liver function despite satisfactory drainage (serum bilirubin persisting at >5 x upper limit of normal for the institution; aspartate aminotransferase or alanine aminotransferase >3.0 x upper limit of normal or >5 x upper limit of normal if liver metastases are present; alkaline phosphatase levels >5.0 x upper limit of normal).
- Inadequate renal function, as determined by local practice for patients on fractionated platinum-based chemotherapy. Patients with creatinine clearance <45 mL/min (in France: <60 mL/min) must not be included.
Other protocol-defined criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PCI treatment in conjunction with Standard of Care (SoC) Fimaporfin and Gemcitabine Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy PCI treatment in conjunction with Standard of Care (SoC) Gemcitabine/Cisplatin chemotherapy Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy Standard of Care (SoC) Gemcitabine/Cisplatin chemotherapy Arm B: Gemcitabine/cisplatin chemotherapy
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Up to 18 months From date of randomisation to date of objective disease progression or death, whichever comes first (in months)
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to 24 months From date of randomisation to date of death from any cause (in months)
Change in Tumor Size Up to 18 months Best overall percentage change in tumour size from baseline
Best Overall Response (BOR) Up to 18 months Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1)
Objective Response Rate (ORR) Up to 18 months Proportion of patients with measurable disease at baseline who have at least one visit response with a complete response (CR) or partial response (PR) noted (according to RECIST 1.1)
Duration of Response (DoR) Up to 24 months From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months)
Adverse Events (AEs)/Serious Adverse Events (SAEs) Up to 12 months Number and proportion of patients with AEs/SAEs
Time to Cmax (Tmax) Was Performed for Patients in Arm A. Timepoints for PK sampling: Day -4 (before, 30 min and 4 hours after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30 min and 4 hours after Amphinex) , C5-D1, and C5-D8 A non-compartmental analysis (NCA) was applied on the data as described by Gabrielsson \& Weiner (Methods in molecular biology, 929:161-180, 2012).
Health-related Quality of Life (QoL) Up to 18 months QoL assessment. Patients select one of four answers to 22 questions ranging from 1 (not at all) to 4 (very much). Lower total scores indicate a more favorable QoL perception than a higher score.
Overall Disease Control Rate (DCR) 6 months and 12 months Proportion of patients with BOR of CR, PR or stable disease (SD) (according to RECIST 1.1) at or after the first follow-up scan, partial response or complete response
Loco-regional Tumour-related Events and Biliary Complications Up to 12 months Frequency and severity of loco-regional tumour related events and biliary complications
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment) A non-compartmental analysis (NCA) was applied on the data. AUC from time zero to the last measured concentration (AUC 0-t) was initially estimated by the linear trapezoidal method.
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. Timepoints for pharmacokinetic (PK) sampling: Day -4 (before, 30m and 4hrs after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30m and 4hrs after Amphinex), C5-D1, and C5-D8 A non-compartmental analysis (NCA) was applied on the data.
Trial Locations
- Locations (50)
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Odense Universitetshospital
🇩🇰Odense, Denmark
The Mayo Clinic Hospital - Saint Mary's Campus, 1216 Second Street Southwest
🇺🇸Rochester, Minnesota, United States
Pusan National University Hospital, 179 Gudeok-ro, Seo-gu
🇰🇷Busan, Korea, Republic of
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Emory University Hospital, 1365C Clifton Road NE
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center, 5841 South Maryland Avenue
🇺🇸Chicago, Illinois, United States
UZ Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon
🇫🇷Grenoble, Cedex 09, France
UZ Leuven
🇧🇪Leuven, Belgium
Tampereen yliopistollinen sairaala, Syöpätautien klinikka
🇫🇮Tampere, Finland
CHU Angers
🇫🇷Angers, Cedex 9, France
Klinikum rechts der Isar der Technischen Universität München
🇩🇪München, Bayern, Germany
Institut Gustave Roussy, Département de gastro-entérologie
🇫🇷Villejuif, France
CHU Dupuytren, 2 Avenue Martin Luther King
🇫🇷Limoges, France
Universitätsklinikum Frankfurt
🇩🇪Frankfurt am main, Hessen, Germany
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Klinikum Landshut
🇩🇪Landshut, Germany
Universität Leipzig KöR
🇩🇪Leipzig, Germany
LAKUMED Kliniken
🇩🇪Landshut, Germany
Klinikum Mannheim Universitätsklinikum gGmbH
🇩🇪Mannheim, Germany
Klinikum der Ludwig-Maximilians-Universität MünchenKlinik
🇩🇪Muenchen, Germany
Azienda Ospedaliero Universitaria Di Modena Policlinico
🇮🇹Modena, Emilia-Romagna, Italy
National Cancer Center, 323 Ilsan-ro, Ilsandong-gu
🇰🇷Goyang-si, Gyeonggido, Korea, Republic of
Klinikum NĂĽrnberg Nord, Medizinische Klinik 6 - (Schwerpunkte Gastroenterologie, Hepatologie, Endokrinologie)
🇩🇪Nürnberg, Germany
IRCCS Saverio de Bellis, Via Turi, 27
🇮🇹Castellana Grotte, Italy
Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Warminsko-mazurskie, Poland
Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu
🇰🇷Seoul, Korea, Republic of
Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu
🇰🇷Daegu, Korea, Republic of
Clinica Universidad Navarra
🇪🇸Pamplona, Navarra, Spain
Severance Hospital Yonsei University Health System, 50-1, Yonsei-Ro, Seodaemun-Gu
🇰🇷Soeul, Korea, Republic of
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Med-Polonia Sp. z o.o.
🇵🇱Poznań, Poland
The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-Daero Seocho-gu
🇰🇷Soeul, Korea, Republic of
Hospital Universitario HM Sanchinarro - CIOCC
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Spain
Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sec. 4
🇨🇳Taichung, Taiwan
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Spain
Karolinska Universitetssjukhuset Solna, P.O Bäckencancer, Karolinska Universitetssjukhuset
🇸🇪Stockholm, Stockholms Ian, Sweden
Taipei Veterans General Hospital, No. 201, Sction 2, Shi-pai Road
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital, Linkou, Dept. of Medical Oncology, 5 Fuxing Street, Guishan
🇨🇳Taoyuan, Taiwan
SI "National Institute of Surgery and Transplantology n.a. O.O. Shalimov " of NAMS of Ukraine
🇺🇦Kyiv, Ukraine
MNPE of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection
🇺🇦Kharkiv, Ukraine
SI Institute for General and Urgent Surgery n.a. V.T. Zaitseva of NAMS of Uktraine
🇺🇦Kharkiv, Ukraine
Universitätsklinikum Hamburg Eppendorf, I. Medizinische Klinik und Poliklinik (Gastroenterologie mit Sektionen Infektiologie und Tropenmediz)
🇩🇪Hamburg, Germany
Municipal Nonprofit Enterprise City Hospital #3 of Zaporizhzhia City Council
🇺🇦Zaporizhzhya, Ukraine
Oslo Universitetssykehus HF Radiumhospitalet
🇳🇴Oslo, Norway