Clinical Trials Register

Summary
EudraCT Number:	2012-002888-10
Sponsor's Protocol Code Number:	PCIA202/12
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-002888-10

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

PCIA202/12

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PCI Biotech AS
B.1.3.4	Country	Norway
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	PCI Biotech AS
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Theradex (Europe) Ltd
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	2nd Floor, The Pinnacle, Station Way
B.5.3.2	Town/ city	Crawley
B.5.3.3	Post code	RH10 1JH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4401293510319
B.5.5	Fax number	+4401293510322
B.5.6	E-mail	regulatory@theradex.co.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/16/1720
D.3 Description of the IMP
D.3.1	Product name	Amphinex
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	fimaporfin
D.3.9.1	CAS number	1443547-43-0
D.3.9.2	Current sponsor code	TPCS2a
D.3.9.3	Other descriptive name	AMPHINEX
D.3.9.4	EV Substance Code	SUB91568
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Gemcitabine
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GEMCITABINE
D.3.9.1	CAS number	95058-81-4
D.3.9.4	EV Substance Code	SUB07892MIG
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Inoperable advanced cholangiocarcinomas

E.1.1.1

Medical condition in easily understood language

Inoperable advanced cholangiocarcinomas

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10008594
E.1.2	Term	Cholangiocarcinoma non-resectable
E.1.2	System Organ Class	100000054936

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

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 two-administration 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

E.2.3

Trial contains a sub-study

E.3

Principal 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

E.4

Principal 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 disease-free 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

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to study protocol

E.5.2

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

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to study protocol

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose escalation

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

PCI procedure + combination chemotherapy vs combination chemotherapy alone

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Care will be at the Investigator's discretion

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-10-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-02-21

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