Clinical trial NCT04099888: PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cholangiocarcinoma
Keywords: Phase II
Safety
Tolerability
Efficacy
Amphinex-induced Photochemical Internalisation
PCI
Amphinex
Gemcitabine
Cisplatin
Inoperable
CCA
Cholangiocarcinoma
Bile duct cancer
Photodynamic therapy
Extrahepatic
Perihilar
Distal
Fimaporfin
Pivotal
RELEASE
PDT
FimaChem
Klatskin
First line treatment
Standard of care
SOC
Chemotherapy
Local treatment
Lead sponsor: PCI Biotech AS
Sponsor class: INDUSTRY
First posted: 2019-09-23
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 18 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Best Overall Response (BOR)
timeFrame: Up to 18 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 18 months
measure: Duration of Response (DoR)
timeFrame: Up to 24 months
measure: Overall Disease Control Rate (DCR)
timeFrame: 6 months and 12 months
measure: Change in Tumor Size
timeFrame: Up to 18 months
measure: Loco-regional Tumour-related Events and Biliary Complications
timeFrame: Up to 12 months
measure: Adverse Events (AEs)/Serious Adverse Events (SAEs)
timeFrame: Up to 12 months
measure: Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A.
timeFrame: Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment)
measure: Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A.
timeFrame: 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
measure: Time to Cmax (Tmax) Was Performed for Patients in Arm A.
timeFrame: 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
measure: Health-related Quality of Life (QoL)
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University Hospital, 1365C Clifton Road NE
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center, 5841 South Maryland Avenue
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Rochester
country: United States
facility: The Mayo Clinic Hospital - Saint Mary's Campus, 1216 Second Street Southwest
state: Minnesota
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala, Syöpätautien klinikka
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon
state: Cedex 09
city: Angers
country: France
facility: CHU Angers
state: Cedex 9
city: Limoges
country: France
facility: CHU Dupuytren, 2 Avenue Martin Luther King
city: Villejuif
country: France
facility: Institut Gustave Roussy, Département de gastro-entérologie
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
state: Bayern
city: Frankfurt am main
country: Germany
facility: Universitätsklinikum Frankfurt
state: Hessen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf, I. Medizinische Klinik und Poliklinik (Gastroenterologie mit Sektionen Infektiologie und Tropenmediz)
city: Landshut
country: Germany
facility: Klinikum Landshut
city: Landshut
country: Germany
facility: LAKUMED Kliniken
city: Leipzig
country: Germany
facility: Universität Leipzig KöR
city: Mannheim
country: Germany
facility: Klinikum Mannheim Universitätsklinikum gGmbH
city: Muenchen
country: Germany
facility: Klinikum der Ludwig-Maximilians-Universität MünchenKlinik
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord, Medizinische Klinik 6 - (Schwerpunkte Gastroenterologie, Hepatologie, Endokrinologie)
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena Policlinico
state: Emilia-Romagna
city: Castellana Grotte
country: Italy
facility: IRCCS Saverio de Bellis, Via Turi, 27
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center, 323 Ilsan-ro, Ilsandong-gu
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital, 179 Gudeok-ro, Seo-gu
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu
city: Soeul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System, 50-1, Yonsei-Ro, Seodaemun-Gu
city: Soeul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital, 222 Banpo-Daero Seocho-gu
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF Radiumhospitalet
city: Olsztyn
country: Poland
facility: Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii
state: Warminsko-mazurskie
city: Poznań
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna, P.O Bäckencancer, Karolinska Universitetssjukhuset
state: Stockholms Ian
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sec. 4
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital, No. 201, Sction 2, Shi-pai Road
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou, Dept. of Medical Oncology, 5 Fuxing Street, Guishan
city: Kharkiv
country: Ukraine
facility: MNPE of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection
city: Kharkiv
country: Ukraine
facility: SI Institute for General and Urgent Surgery n.a. V.T. Zaitseva of NAMS of Uktraine
city: Kyiv
country: Ukraine
facility: SI "National Institute of Surgery and Transplantology n.a. O.O. Shalimov " of NAMS of Ukraine
city: Zaporizhzhya
country: Ukraine
facility: Municipal Nonprofit Enterprise City Hospital #3 of Zaporizhzhia City Council
Study officials:
affiliation: PCI Biotech
name: PCI Biotech
role: STUDY_DIRECTOR
References: