A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomas

• Register: EUCTR
• Last refreshed on: 12 July 2021
• Main ID: EUCTR2012-002888-10-DE
• Date of registration: 04/12/2012
• Prospective Registration: Yes
• Primary sponsor: PCI Biotech AS
• Public title: A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomas
• Scientific title: A Phase I/II Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of Amphinex®-induced Photochemical Internalisation (PCI) of Gemcitabine Followed by Gemcitabine/Cisplatin Chemotherapy in Patients with Advanced Inoperable Cholangiocarcinomas
• Date of first enrolment: 19/02/2013
• Target sample size: 68
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002888-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: PCI procedure + combination chemotherapy vs combination chemotherapy alone Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Lithuania, Norway, United Kingdom

Contacts

• Name: Regulatory Affairs
• Affiliation: Theradex (Europe) Ltd

• Name: Regulatory Affairs
• Affiliation: Theradex (Europe) Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histopathologically/cytologically (C5) verified adenocarcinoma
consistent with cholangiocarcinoma.
2. Cholangiocarcinoma that:
A) Is considered to be inoperable
B) Has a primary lesion in the perihilar biliary duct region that requires
stent placement
C) Has nodal enlargement =to N1 as per computed
tomography/magnetic resonance imaging assessment
D) If has metastatic disease, this should be confined to the liver
parenchyma only
3. Adequate biliary drainage (either at least 50% of the liver volume, or
at least two sectors), with no evidence of active uncontrolled infection
(patients on antibiotics are eligible)
4. Age =18 years
5. The Eastern Cooperative Oncology Group performance status =1
6. Estimated life expectancy of at least 12 weeks
7. Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Any prior anti-cancer (either local or systemic) treatment for
cholangiocarcinoma
2. Patients with extra-hepatic metastatic cholangiocarcinoma
3. Patients with a severe visceral disease other than
cholangiocarcinoma.
4. Patients with primary sclerosing cholangitis
5. Patients with porphyria or hypersensibility to porphyrins
6. Patients with an active second primary cancer, with exception of
adequately treated basal cell carcinoma, squamous cell carcinoma or
other non-melanomatous skin cancer, or in-situ carcinoma of the uterine
cervix. An active second primary cancer is defined as one with a diseasefree
interval of <5 years before registration/randomisation.
7. Inability to undergo computed tomography or magnetic resonance
imaging
8. Current participation in any other interventional clinical trial
9. Male patients not willing to use adequate contraception or female
patients of childbearing potential not willing to use an effective form of
contraception such as hormonal birth control, intrauterine device or
double barrier method during PCI treatment and subsequent
chemotherapy and for at least 6 months thereafter.
10. Breast feeding women or women with a positive pregnancy test at
baseline
11. Inadequate bone marrow function:
- Absolute neutrophil count: <1.5 x 109/L, or platelet count <100 x
109/L or haemoglobin <6 mmol/L (transfusion allowed)
12. Inadequate liver function, defined as:
- Serum (total) bilirubin >2.5 x the upper limit of normal for the
institution
- Aspartate amino transferase or alanine amino transferase >3.0 x upper limit of normal (>5.0 x upper limit of normal if liver metastases are
present)
- Alkaline phosphatase levels >5.0 x upper limit of normal
13. Inadequate renal function, defined as:
- Creatinine clearance <60 mL/min
14. Planned surgery, endoscopic examination or dental treatment in the
first 30 days after PCI treatment
15. Co-existing ophthalmic disease likely to require slit-lamp
examination within the first 90 days after PCI treatment
16. Clinically significant and uncontrolled cardiac disease including
unstable angina, acute myocardial infarction within 6 months prior to
baseline, congestive heart failure, and arrhythmia requiring therapy,
with the exception of extra systoles or minor conduction abnormalities
and controlled and well treated chronic atrial fibrillation
17. Known allergy or sensitivity to photosensitisers
18. Ataxia telangiectasia
19. Evidence of any other medical conditions (such as psychiatric illness,
infectious diseases, 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
20. Significant hearing impairment
21. Patients concurrently receiving phenytoin
22. Patients defined as vulnerable according to French law (France only,
also see Section 5.4


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Inoperable locally advanced cholangiocarcinomas
MedDRA version: 20.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864

Intervention(s)

Product Name: Amphinex
Pharmaceutical Form: Solution for injection
INN or Proposed INN: fimaporfin
CAS Number: 1443547-43-0
Current Sponsor code: TPCS2a
Other descriptive name: AMPHINEX
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4

Primary Outcome(s)

Secondary Objective: Phase I Dose Escalation
• To characterise the pharmacokinetic profiles of Amphinex and
gemcitabine
• To make a preliminary assessment of the efficacy of Amphinex-induced
PCI of gemcitabine followed by systemic gemcitabine/cisplatin
chemotherapy in patients with advanced inoperable cholangiocarcinoma

Extended Part of Phase I
• To characterise the pharmacokinetic profiles of Amphinex and
gemcitabine
• To make a preliminary assessment of the efficacy of a twoadministration
schedule of Amphinex-induced PCI of gemcitabine
followed by systemic gemcitabine/cisplatin chemotherapy in patients
with advanced inoperable cholangiocarcinoma

Phase II
• To characterise the pharmacokinetic profile of Amphinex
• To further assess the safety and efficacy profile of Amphinex-induced
PCI of gemcitabine followed by the systemic gemcitabine/cisplatin
combination

Primary end point(s): Phase I Dose Escalation (Safety)
• Dose-limiting toxicities and the safety profile (adverse events,
laboratory assessments and physical findings) of the Amphinex-induced
PCI of gemcitabine followed by the gemcitabine/cisplatin combination

Extended Part of Phase I (Safety)
• Schedule-limiting toxicities and the safety profile (adverse events,
laboratory assessments and physical findings) of a two-administration
schedule of Amphinex-induced PCI of gemcitabine followed by systemic
gemcitabine/cisplatin chemotherapy

Phase II (Efficacy)
• Progression-free survival, defined as the time from randomisation to
documented disease progression (according to Response Evaluation
Criteria in Solid Tumours [RECIST] 1.1 criteria) or death from any cause.

Main Objective: Phase I Dose Escalation
• To determine a tolerable dose and safety profile of Amphinex-induced
PCI of gemcitabine followed by systemic gemcitabine/cisplatin
chemotherapy in patients with advanced inoperable cholangiocarcinoma

Extended Part of Phase I
• To determine the tolerability and safety profile of a two-administration
schedule of Amphinex-induced PCI of gemcitabine followed by systemic
gemcitabine/cisplatin chemotherapy in patients with advanced
inoperable cholangiocarcinoma

Phase II
• To make a preliminary assessment of the efficacy of Amphinex-induced
PCI of gemcitabine followed by systemic gemcitabine/cisplatin
chemotherapy in patients with advanced inoperable cholangiocarcinoma

Timepoint(s) of evaluation of this end point: Please refer to study protocol

Secondary Outcome(s)

Secondary end point(s): Phase I Dose Escalation
• Pharmacokinetic profile of Amphinex and gemcitabine in plasma
• Progression-free survival, defined as the time from registration to
documented disease progression (according to RECIST 1.1 criteria) or
death from any cause
• Best overall response

Extended Part of Phase I
• Pharmacokinetic profile of Amphinex and gemcitabine in plasma
• Progression-free survival, defined as the time from registration to
documented disease progression (according to RECIST 1.1 criteria) or death from any cause
• Best overall response at 24 weeks

Phase II
• Overall response rate, calculated as the proportion of patients with a
best overall response of confirmed complete response or partial
response
• Disease control rate, defined as the proportion of patients with best
overall response of confirmed complete response, partial response or
stable disease
• Overall survival, calculated as the time from randomisation to the date
of death from any cause
• Best overall response
• Pharmacokinetic profile of Amphinex in bile
• Safety profile (adverse events, laboratory assessments and physical
findings) of the Amphinex-induced PCI of gemcitabine followed by the
gemcitabine/cisplatin combination, or the gemcitabine/cisplatin
combination alone

Timepoint(s) of evaluation of this end point: Please refer to study protocol

Secondary ID(s)

2012-002888-10-GB

PCIA202/12

Source(s) of Monetary Support

PCI Biotech AS

Ethics review

Status: Approved
Approval date: 19/02/2013
Contact:

Results

• Results available: Yes
• Date Posted: 23/05/2021
• Date Completed: 21/02/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002888-10/results