Clinical Trials Register

Summary
EudraCT Number:	2011-003194-28
Sponsor's Protocol Code Number:	PULSION-001
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-08
Trial 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

Germany - BfArM

A.2

EudraCT number

2011-003194-28

A.3

Full title of the trial

Determination of the sensitivity of ICG fluorescence technique for the detection of Sentinel Lymph Nodes in breast cancer – a monocenter, prospective open-label clinical trial

A.3.1

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

ICG fluorescence technique for the detection of Sentinel Lymph Nodes

A.3.2

Name or abbreviated title of the trial where available

PULSION-001

A.4.1

Sponsor's protocol code number

PULSION-001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01395706

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	PULSION Medical Systems SE
B.1.3.4	Country	Germany
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	PULSION Medical Systems SE
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PULSION Medical Systems Se
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Joseph-wild-Strasse 20
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	81829
B.5.3.4	Country	Germany
B.5.4	Telephone number	++4989459914501
B.5.5	Fax number	++4989459914508
B.5.6	E-mail	puehler@pulsion.com

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	Yes
D.2.1.1.1	Trade name	ICG-PULSION®
D.2.1.1.2	Name of the Marketing Authorisation holder	PULSION Medical Systems SE
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	ICG-PULSION
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Indocyaningrün
D.3.9.1	CAS number	3599-32-4
D.3.9.3	Other descriptive name	INDOCYANINE GREEN
D.3.9.4	EV Substance Code	SUB14208MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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	Yes
D.3.11.13.1	Other medicinal product type	Medicinal product is a fluorescence dye for diagnostic
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.1.1	Trade name	Nanocoll®
D.2.1.1.2	Name of the Marketing Authorisation holder	GE Healthcare Buchler GmbH & Co KG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	99m Tc Nanocoll®
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subdermal use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Humanalbumin
D.3.9.3	Other descriptive name	TECHNETIUM (99MTC) HUMAN ALBUMIN
D.3.9.4	EV Substance Code	SUB12349MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
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	Yes
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

Breast cancer with indicated sentinel lymph node biopsy.

E.1.1.1

Medical condition in easily understood language

Breast cancer

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of this clinical trial is to show the efficacy of fluorescence lymphangiography with indocyanine green (ICG) for the detection of sentinel lymph nodes.

E.2.2

Secondary objectives of the trial

The safety and tolerability of this method is to be assessed.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Early breast cancer: histopathologically confirmed diagnosis, maximum tumour stage T1 and T2, therefore diameter < 5 cm, unifocal tumour or multifocal tumour Grading G1-G3

Indicated sentinel lymph node biopsy as part of the patient’s routine management for breast cancer

Age: 18 – 80 years, inclusive

Gender: male and female

General operability

Intact site-specific anatomy at the concerned breast and /or axilla for ensuring an adequate lymphangiography

if a performance of investigations with radioactive traced iodide is planed, this has to be performed at least 1 week before or 1 week after ICG application

No clinically significant findings in the routine blood examinations

Female subjects must be either at least two years postmenopausal or must have a negative pregnancy test prior to Tc application and must use a highly effective means of birth control (birth control that, alone or in combination, result in a low failure rate of less than 1% per year when used consistently and correctly):
hormonal method of contraceptive,
surgical sterility,
double barrier methods,
intrauterine contraceptive device,
lifestyle with a personal choice of abstinence,
bilateral vasectomy of sexual partner at least 3 months prior to
enrolment in combination with barrier methods

Willing and able to complete screening and study procedures, as described in the protocol

Signed written informed consent to participate in this clinical trial

E.4

Principal exclusion criteria

Breast cancer: stage T3 or T4 carcinoma, inflammatory or exulcerated mamma carcinoma

Former operation in axilla

Any previous radiotherapy at the concerned breast and / or axilla and / or chestwall

Definite lymph node metastases (ultrasound and / or fine-needle aspiration) (definite nodal positive patients in fine-needle aspiration)

Contraindication for technetium imaging

History of allergy or hypersensitivity against the investigational medicinal products (its active substance or ingredients)

History of intolerability to ICG-Pulsion® during a previous injection, as this may lead to serious anaphylactic reactions

History of allergic diseases / hypersensitivities, unless the investigator considers the allergic disease as clinically irrelevant for the purpose of this clinical trial

Allergy to iodine or to shellfish

Any other contraindication to one of the investigational medicinal products as described in their Summary of Product Characteristics

Apparent hyperthyroidism, autonomous thyroid adenoma, unifocal, multifocal or disseminated autonomies of the thyroid gland

Advanced renal impairment (creatinine > 1,5mg/dl)

Complete lymphatic obstruction

All clinically relevant internal medicinal diseases, cardiac or renal that could impair the outcome of the clinical trial or that in the investigator’s mind are not compatible with participation for medical reasons

Acute inflammatory or febrile illness

Evidence of local inflammation at the site of surgery

Concurrent medication or any medication during the 2 weeks preceeding the enrolment which reduce or increase the extinction of ICG (i.e. anticonvulsants, haloperidol)

Current or recent history of illicit drug or alcohol abuse, or dependence as defined as the continued use of alcohol or drugs despite the development of social, legal, or health problems

Psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the subject’s ability to comply with the study requirements (e.g. Alzheimer’s disease)

Pregnancy, breastfeeding

Inability to understand the nature and the extent of the trial and the procedures required

Missing signed written informed consent to participate in the clinical trial

Participation in a drug trial during the whole clinical trial

E.5 End points

E.5.1

Primary end point(s)

Sensitivity using ICG:
Intraindividual: number of tumor-involved fluorescent lymph nodes / total number tumor-involved, Technetium positive sentinel lymph nodes OR
Intraindividual: all tumor – involved, Tc positive SLN must also be fluorescent OR
Interindividual: number of patients with tumor – involved, fluorescent LN / total numbers of patients with tumor-involved, Tc positive SLN

Specificity using ICG:
number patients with fluorescent lymph nodes that are not tumor – involved / number of patients with Tc positive SLN OR
all Tc positive SLN are not tumor – involved and are also fluorescent

False negative rate:
Number of patients where no lymph node is detected neiter with Tc nor with ICG but in the control scintigraphy

Detection rate for the SLN using the ICG fluorescence imaging method:
number of patients with at least one fluorescent sentinel lymph node per total number of patients treated with ICG

E.5.1.1

Timepoint(s) of evaluation of this end point

At visit 3, directly after the injection during the surgery

E.5.2

Secondary end point(s)

Safety and tolerability of ICG

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

This clinical trial will end with the final examination of the last clinical trial participant.

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:

125

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

125

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

125

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)

The treatment and care after the patient has ended the participation in the clinical trial will be in accordance with the individual medical findings as well as the discretion of the investigator and the agreement of the patient.

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

2011-10-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-01-12

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