PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer

NCT ID: NCT04099888

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-23
• Study Completion Date: 2022-05-06

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.

Conditions

Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PCI treatment in conjunction with Standard of Care (SoC)

Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy

Group Type: EXPERIMENTAL

Fimaporfin and Gemcitabine

Intervention Type: DRUG

PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given.

Gemcitabine/Cisplatin chemotherapy

Intervention Type: DRUG

Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.

Standard of Care (SoC)

Arm B: Gemcitabine/cisplatin chemotherapy

Group Type: ACTIVE_COMPARATOR

Gemcitabine/Cisplatin chemotherapy

Intervention Type: DRUG

Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.

Interventions

Fimaporfin and Gemcitabine

PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given.

Intervention Type: DRUG

Gemcitabine/Cisplatin chemotherapy

Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.

Intervention Type: DRUG

Other Intervention Names

PCI treatment; Standard of care (SoC)

Eligibility Criteria

Inclusion Criteria

1. Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements.

2. 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).

3. CCA must be considered inoperable with respect to radical resection.

4. At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation.

5. If metastatic, metastases must be limited tissues other than bone or the central nervous system.

6. 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).

7. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Estimated life expectancy of at least 12 weeks.

Exclusion Criteria

1. 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.

2. Patients with severe visceral disease other than CCA.

3. A history of frequently recurring septic biliary events.

4. Patients with porphyria or hypersensitivity to porphyrins.

5. 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.

6. Patients not able to undergo contrast-enhanced CT or MRI.

7. Patients currently participating in any other interventional clinical trial.

8. Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment.

9. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment.

10. Clinically significant and uncontrolled cardiac disease except for extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation.

11. 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.

12. Known hypersensitivity to or contraindication to the use of gemcitabine (active substance and/or any of the excipients).

13. Known hypersensitivity to or contraindication to the use of cisplatin (active substance and/or any of the excipients).

14. Patients with ataxia telangiectasia.

15. 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.

16. Patients planning to have or who have recently had vaccination with a live vaccine.

17. Patients concurrently receiving treatment with phenytoin.

18. 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.

19. Women who are breastfeeding or who have a positive pregnancy test at baseline.

20. 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]).

21. 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).

22. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PCI Biotech AS

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

PCI Biotech

Role: STUDY_DIRECTOR

PCI Biotech

Locations

City of Hope National Medical Center

Duarte, California, 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

University of Louisville

Louisville, Kentucky, United States

The Mayo Clinic Hospital - Saint Mary's Campus, 1216 Second Street Southwest

Rochester, Minnesota, United States

Baylor College of Medicine

Houston, Texas, United States

UZ Gent

Ghent, Oost-Vlaanderen, Belgium

UZ Leuven

Leuven, , Belgium

Odense Universitetshospital

Odense, , Denmark

Tampereen yliopistollinen sairaala, Syöpätautien klinikka

Tampere, , Finland

Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon

Grenoble, Cedex 09, France

CHU Angers

Angers, Cedex 9, France

CHU Dupuytren, 2 Avenue Martin Luther King

Limoges, , France

Institut Gustave Roussy, Département de gastro-entérologie

Villejuif, , France

Klinikum rechts der Isar der Technischen Universität München

München, Bavaria, Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Universitätsklinikum Bonn

Bonn, , Germany

Universitätsklinikum Hamburg Eppendorf, I. Medizinische Klinik und Poliklinik (Gastroenterologie mit Sektionen Infektiologie und Tropenmediz)

Hamburg, , Germany

Klinikum Landshut

Landshut, , Germany

LAKUMED Kliniken

Landshut, , Germany

Universität Leipzig KöR

Leipzig, , Germany

Klinikum Mannheim Universitätsklinikum gGmbH

Mannheim, , Germany

Klinikum der Ludwig-Maximilians-Universität MünchenKlinik

München, , Germany

Klinikum Nürnberg Nord, Medizinische Klinik 6 - (Schwerpunkte Gastroenterologie, Hepatologie, Endokrinologie)

Nuremberg, , Germany

Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, Emilia-Romagna, Italy

IRCCS Saverio de Bellis, Via Turi, 27

Castellana Grotte, , Italy

Oslo Universitetssykehus HF Radiumhospitalet

Oslo, , Norway

Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii

Olsztyn, Warmian-Masurian Voivodeship, Poland

Med-Polonia Sp. z o.o.

Poznan, , Poland

National Cancer Center, 323 Ilsan-ro, Ilsandong-gu

Goyang-si, Gyeonggido, South Korea

Pusan National University Hospital, 179 Gudeok-ro, Seo-gu

Busan, , South Korea

Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu

Daegu, , South Korea

Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu

Seoul, , South Korea

Severance Hospital Yonsei University Health System, 50-1, Yonsei-Ro, Seodaemun-Gu

Soeul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-Daero Seocho-gu

Soeul, , South Korea

Clinica Universidad Navarra

Pamplona, Navarre, Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario HM Sanchinarro - CIOCC

Madrid, , Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, , Spain

Corporacio Sanitaria Parc Tauli

Sabadell, , Spain

Karolinska Universitetssjukhuset Solna, P.O Bäckencancer, Karolinska Universitetssjukhuset

Stockholm, Stockholms Ian, Sweden

Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sec. 4

Taichung, , Taiwan

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 District, , Taiwan

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

SI "National Institute of Surgery and Transplantology n.a. O.O. Shalimov " of NAMS of Ukraine

Kyiv, , Ukraine

Municipal Nonprofit Enterprise City Hospital #3 of Zaporizhzhia City Council

Zaporizhzhya, , Ukraine

Countries

United States; Belgium; Denmark; Finland; France; Germany; Italy; Norway; Poland; South Korea; Spain; Sweden; Taiwan; Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PCIA 203/18

Identifier Type: -

Identifier Source: org_study_id