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

Sponsor

PCI Biotech AS (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04099888

Collaborator

(none)

Enrollment

Locations

Arms

82.3

Anticipated Duration (Months)

0.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cholangiocarcinoma	Drug: Fimaporfin and Gemcitabine Drug: Gemcitabine/Cisplatin chemotherapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 23, 2019

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PCI treatment in conjunction with Standard of Care (SoC) Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy	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. Other Names: PCI treatment Drug: Gemcitabine/Cisplatin chemotherapy Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered. Other Names: Standard of care (SoC)
Active Comparator: Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy	Drug: Gemcitabine/Cisplatin chemotherapy Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered. Other Names: Standard of care (SoC)

Arm

Intervention/Treatment

Experimental: PCI treatment in conjunction with Standard of Care (SoC)

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

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.

Other Names:

PCI treatment

Drug: Gemcitabine/Cisplatin chemotherapy

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

Other Names:

Standard of care (SoC)

Active Comparator: Standard of Care (SoC)

Arm B: Gemcitabine/cisplatin chemotherapy

Drug: Gemcitabine/Cisplatin chemotherapy

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

Other Names:

Standard of care (SoC)

Outcome Measures

Primary Outcome Measures

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

Overall survival (OS) [Up to 24 months]
From date of randomisation to date of death from any cause (in months)
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 CR (complete response) or PR (partial response) 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)
Disease Control Rate (DCR) [At 6 months and 12 months]
Proportion of patients with BOR of CR, PR or SD (stable disease) (according to RECIST 1.1)
Change in tumor size [Up to 18 months]
Best overall percentage change in tumour size from baseline (in millimeters (mm))
Loco-regional tumour-related events and biliary complications [Up to 12 months]
Frequency and severity of loco-regional tumour related events and biliary complications
Adverse Events (AEs)/Serious Adverse Events (SAEs) [Up to 12 months]
Number and proportion of patients with AEs/SAEs
Area under the plasma concentration curve (AUC) [Up to 12 months]
In Arm A patients
Maximum observed concentration (Cmax) [Up to 12 months]
In Arm A patients
Time to Cmax (Tmax) [Up to 12 months]
In Arm A patients
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Emory University Hospital, 1365C Clifton Road NE	Atlanta	Georgia	United States	30322
3	University of Chicago Medical Center, 5841 South Maryland Avenue	Chicago	Illinois	United States	60637
4	University of Louisville	Louisville	Kentucky	United States	40202
5	The Mayo Clinic Hospital - Saint Mary's Campus, 1216 Second Street Southwest	Rochester	Minnesota	United States	55902
6	Baylor College of Medicine	Houston	Texas	United States	77096
7	UZ Gent	Gent	Oost-Vlaanderen	Belgium	9000
8	UZ Leuven	Leuven		Belgium	3000
9	Odense Universitetshospital	Odense		Denmark	5000
10	Tampereen yliopistollinen sairaala, Syöpätautien klinikka	Tampere		Finland	FI-33520
11	Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon	Grenoble	Cedex 09	France	38043
12	CHU Angers	Angers	Cedex 9	France	49933
13	CHU Dupuytren, 2 Avenue Martin Luther King	Limoges		France	87042
14	Institut Gustave Roussy, Département de gastro-entérologie	Villejuif		France	94805
15	Klinikum rechts der Isar der Technischen Universität München	München	Bayern	Germany	81675
16	Universitätsklinikum Frankfurt	Frankfurt am main	Hessen	Germany	60590
17	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany	45122
18	Universitätsklinikum Bonn	Bonn		Germany	53105
19	Universitätsklinikum Hamburg Eppendorf, I. Medizinische Klinik und Poliklinik (Gastroenterologie mit Sektionen Infektiologie und Tropenmediz)	Hamburg		Germany	20246
20	Klinikum Landshut	Landshut		Germany	84034
21	LAKUMED Kliniken	Landshut		Germany	84036
22	Universität Leipzig KöR	Leipzig		Germany	04103
23	Klinikum Mannheim Universitätsklinikum gGmbH	Mannheim		Germany	68167
24	Klinikum der Ludwig-Maximilians-Universität MünchenKlinik	Muenchen		Germany	81377
25	Klinikum Nürnberg Nord, Medizinische Klinik 6 - (Schwerpunkte Gastroenterologie, Hepatologie, Endokrinologie)	Nürnberg		Germany	90419
26	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena	Emilia-Romagna	Italy	41100
27	IRCCS Saverio de Bellis, Via Turi, 27	Castellana Grotte		Italy	70013
28	National Cancer Center, 323 Ilsan-ro, Ilsandong-gu	Goyang-si	Gyeonggido	Korea, Republic of	10408
29	Pusan National University Hospital, 179 Gudeok-ro, Seo-gu	Busan		Korea, Republic of	49241
30	Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu	Daegu		Korea, Republic of	41404
31	Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu	Seoul		Korea, Republic of	05505
32	Severance Hospital Yonsei University Health System, 50-1, Yonsei-Ro, Seodaemun-Gu	Soeul		Korea, Republic of	03722
33	The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-Daero Seocho-gu	Soeul		Korea, Republic of	06591
34	Oslo Universitetssykehus HF Radiumhospitalet	Oslo		Norway
35	Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii	Olsztyn	Warminsko-mazurskie	Poland	10-228
36	Med-Polonia Sp. z o.o.	Poznań		Poland	60-569
37	Clinica Universidad Navarra	Pamplona	Navarra	Spain	31008
38	Hospital del Mar	Barcelona		Spain	08033
39	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
40	Hospital Universitario HM Sanchinarro - CIOCC	Madrid		Spain	28050
41	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda		Spain	28222
42	Corporacio Sanitaria Parc Tauli	Sabadell		Spain	08208
43	Karolinska Universitetssjukhuset Solna, P.O Bäckencancer, Karolinska Universitetssjukhuset	Stockholm	Stockholms Ian	Sweden	SE-17176
44	Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sec. 4	Taichung		Taiwan	40705
45	Taipei Veterans General Hospital, No. 201, Sction 2, Shi-pai Road	Taipei		Taiwan	11217
46	Chang Gung Memorial Hospital, Linkou, Dept. of Medical Oncology, 5 Fuxing Street, Guishan	Taoyuan		Taiwan	33305
47	MNPE of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection	Kharkiv		Ukraine
48	SI Institute for General and Urgent Surgery n.a. V.T. Zaitseva of NAMS of Uktraine	Kharkiv		Ukraine
49	SI "National Institute of Surgery and Transplantology n.a. O.O. Shalimov " of NAMS of Ukraine	Kyiv		Ukraine
50	Municipal Nonprofit Enterprise City Hospital #3 of Zaporizhzhia City Council	Zaporizhzhya		Ukraine