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

Cholangiocarcinoma Clinical Trial

— RELEASE  

Official title:

A Multi-Center Randomised Open-Label Phase 2 Study to Assess the Safety, Tolerability and Efficacy of Fimaporfin-Induced Photochemical Internalisation of Gemcitabine Complemented by Gemcitabine/Cisplatin Chemotherapy Versus Gemcitabine/Cisplatin Alone in Patients With Inoperable Cholangiocarcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04099888
• Other study ID #: PCIA 203/18
• Status: Terminated
• Phase: Phase 2
• Start date: May 23, 2019
• Est. completion date: May 6, 2022

Study information

• Verified date: April 2023
• Source: PCI Biotech AS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: May 6, 2022
• Est. primary completion date: April 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholangiocarcinoma

Intervention

Drug:
• 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.
• Gemcitabine/Cisplatin chemotherapy
Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	UZ Leuven	Leuven
Denmark	Odense Universitetshospital	Odense
Finland	Tampereen yliopistollinen sairaala, Syöpätautien klinikka	Tampere
France	CHU Angers	Angers	Cedex 9
France	Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon	Grenoble	Cedex 09
France	CHU Dupuytren, 2 Avenue Martin Luther King	Limoges
France	Institut Gustave Roussy, Département de gastro-entérologie	Villejuif
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Frankfurt	Frankfurt am main	Hessen
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	Muenchen
Germany	Klinikum rechts der Isar der Technischen Universität München	München	Bayern
Germany	Klinikum Nürnberg Nord, Medizinische Klinik 6 - (Schwerpunkte Gastroenterologie, Hepatologie, Endokrinologie)	Nürnberg
Italy	IRCCS Saverio de Bellis, Via Turi, 27	Castellana Grotte
Italy	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena	Emilia-Romagna
Korea, Republic of	Pusan National University Hospital, 179 Gudeok-ro, Seo-gu	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu	Daegu
Korea, Republic of	National Cancer Center, 323 Ilsan-ro, Ilsandong-gu	Goyang-si	Gyeonggido
Korea, Republic of	Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System, 50-1, Yonsei-Ro, Seodaemun-Gu	Soeul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-Daero Seocho-gu	Soeul
Norway	Oslo Universitetssykehus HF Radiumhospitalet	Oslo
Poland	Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii	Olsztyn	Warminsko-mazurskie
Poland	Med-Polonia Sp. z o.o.	Poznan
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	Clinica Universidad Navarra	Pamplona	Navarra
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Sweden	Karolinska Universitetssjukhuset Solna, P.O Bäckencancer, Karolinska Universitetssjukhuset	Stockholm	Stockholms Ian
Taiwan	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
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	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
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	City of Hope National Medical Center	Duarte	California
United States	Baylor College of Medicine	Houston	Texas
United States	University of Louisville	Louisville	Kentucky
United States	The Mayo Clinic Hospital - Saint Mary's Campus, 1216 Second Street Southwest	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
PCI Biotech AS

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  Finland,  France,  Germany,  Italy,  Korea, Republic of,  Norway,  Poland,  Spain,  Sweden,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	From date of randomisation to date of objective disease progression or death, whichever comes first (in months)	Up to 18 months
Secondary	Overall Survival (OS)	From date of randomisation to date of death from any cause (in months)	Up to 24 months
Secondary	Best Overall Response (BOR)	Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1)	Up to 18 months
Secondary	Objective Response Rate (ORR)	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)	Up to 18 months
Secondary	Duration of Response (DoR)	From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months)	Up to 24 months
Secondary	Overall Disease Control Rate (DCR)	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	6 months and 12 months
Secondary	Change in Tumor Size	Best overall percentage change in tumour size from baseline	Up to 18 months
Secondary	Loco-regional Tumour-related Events and Biliary Complications	Frequency and severity of loco-regional tumour related events and biliary complications	Up to 12 months
Secondary	Adverse Events (AEs)/Serious Adverse Events (SAEs)	Number and proportion of patients with AEs/SAEs	Up to 12 months
Secondary	Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A.	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.	Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment)
Secondary	Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A.	A non-compartmental analysis (NCA) was applied on the data.	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
Secondary	Time to Cmax (Tmax) Was Performed for Patients in Arm A.	A non-compartmental analysis (NCA) was applied on the data as described by Gabrielsson & Weiner (Methods in molecular biology, 929:161-180, 2012).	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
Secondary	Health-related Quality of Life (QoL)	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.	Up to 18 months