Clinical Trials Register

Summary
EudraCT Number:	2011-004220-34
Sponsor's Protocol Code Number:	TNPET01
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:	2011-12-05
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2011-004220-34

A.3

Full title of the trial

A randomised phase II trial of [18F]fluorothymidine and the standard tracer [18F]Fluorodeoxyglucose in the assessment of systemic therapy response in triple negative breast cancer and their utility compared to conventional MRI imaging response, early ADC change and biopsy derived biomarkers

A.3.1

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

A trial to test two radioactive tracers compared to standard imaging (MRI) when assessing how effective treatment for Breast cancer has been.

A.3.2

Name or abbreviated title of the trial where available

TNBC:Novel functional imaging to determine early chemotherapy response

A.4.1

Sponsor's protocol code number

TNPET01

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	King's College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Guys and St Thomas' Charity
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PET Imaging Centre
B.5.2	Functional name of contact point	PET Imaging Centre
B.5.3	Address:
B.5.3.1	Street Address	St.Thomas’ Hospital, Lambeth Palace Road
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE1 7EH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4402071884988
B.5.5	Fax number	+4402076200790
B.Sponsor: 2
B.1.1	Name of Sponsor	Guy's and St Thomas' NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Guy's and St Thomas' charity
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PET Imaging Centre
B.5.2	Functional name of contact point	PET Imaging Centre
B.5.3	Address:
B.5.3.1	Street Address	St.Thomas’ Hospital, Lambeth Palace Road
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE1 7EH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4402071884988
B.5.5	Fax number	+4402076200790

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	[18F]Fluorothymidine
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	3'-deoxy-3'-[18F]fluorothymidine
D.3.9.3	Other descriptive name	FLT
D.3.10	Strength
D.3.10.1	Concentration unit	MBq megabecquerel(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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.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.2.1.1.1	Trade name	MetaTrace FDG
D.2.1.1.2	Name of the Marketing Authorisation holder	Siemens PLC
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	MetaTrace FDG
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	FLUORINE (18F) FLUDEOXYGLUCOSE
D.3.9.1	CAS number	105851-17-0
D.3.9.4	EV Substance Code	SUB07680MIG
D.3.10	Strength
D.3.10.1	Concentration unit	MBq megabecquerel(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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

Triple Negative Breast Cancer

E.1.1.1

Medical condition in easily understood language

Breast cancer subtype that does not express hormone or HER2 receptors

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10006192
E.1.2	Term	Breast cancer NOS
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A: To confirm repeatability of Positron Emission Tomography (PET) scan SUV measurement before chemotherapy in triple negative breast cancer using [18F]FLT and [18F]FDG tracers
Parts A and B:
To evaluate PET imaging using [18F]FLT or [18F]FDG as a method for evaluating response to systemic therapy in primary triple negative breast cancer

E.2.2

Secondary objectives of the trial

1. optimal scan time post FDG and FLT tracer injection 2. correlate PET imaging response in breast and axillary nodes with residual cancer burden at definitive surgery 3. correlate PET functional imaging changes (SUV response) with changes in biopsy derived markers of proliferation and apoptosis changes
4.assessment of Ki and K1 for each tracer 5. To assess nodal response using PET imaging 6. confirm the safety of FLT 7. To obtain performance estimates for the ability of the Part B tracer (FDG or FLT) response derived from integration of Apparent Diffusion Coefficient (ADC) and size change data at 3 cycles 8. To obtain exploratory performance estimates for ADC change after 1 cycle to report RECIST response after 3 cycles 9. To correlate ADC change with biopsy derived proliferation and apoptosis biomarkers

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Female age 18 to 70 years
• Women of childbearing potential must have documented negative pregnancy test within the 2 weeks prior to day 1 chemotherapy and agree to use a medically acceptable birth control during the duration of their chemotherapy.
• Stage II-III biopsy proven early breast cancer for which primary chemotherapy is recommended. Staging performed in accordance with local protocols.
• All patients will have HER2 negative primary tumours (IHC 0 or 1+, or IHC 2+ and FISH non-amplified (ratio of Her2 to chromosome 17 of more than 2.0)
• All patients will have ER negative primary invasive breast cancer (Allred <3)
• ECOG PS of 0 or 1
• Primary tumour size >2cm
• Eligible for neoadjuvant chemotherapy according to departmental protocols
• Written informed consent
• Able to comply with treatment plans, scheduled visits, all study PET imaging and biopsy procedures and follow-up

E.4

Principal exclusion criteria

• Any prior treatment for the breast cancer
• Patients who are pregnant will be excluded.
• Patients who are breast feeding
• Evidence of metastasic disease at diagnosis precluding neoadjuvant chemotherapy.
• Requirement for concurrent radiotherapy treatment
• Serious medical condition or concurrent medical illness likely to compromise ability to complete prescribed chemotherapy course.
• Anticoagulation requirement which would preclude serial biopsy
• Diabetes Mellitus
• Any other problems that may make the patient unable to tolerate the PET scans or translational biopsies
• Investigational Medicinal Product in the previous 28 days

E.5 End points

E.5.1

Primary end point(s)

Part A
Repeatability for both tracers will be within 20% (second scan at 3 days after first PET +/- 10% of baseline)
Part B
Correlation of SUV response for each tracer with conventional MRI RECIST response assessment after 3 cycles neoadjuvant chemotherapy

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A
second scan at 3 days
Part B
after 3 cycles neoadjuvant chemotherapy

E.5.2

Secondary end point(s)

The Time point in triple negative breast cancer where tumour SUV peaks
Residual cancer burden in breast and axilla
Correlation with percentage cells positive for proliferation markers Ki-67 (MIB1), geminin, mcms and tunel apoptosis assay, tumour genotype and mRNA expression markers of proliferation genes in residual tumour (if present).
The dynamic analysis will use an input function derived from the aorta or the heart or both to derive rate constants Ki and k1, measurements of transport of and phosphorylation for both tracers
Correlate SUV response in the nodes with SUV response in the breast primary
Evaluate the ability of FDG and FLT tracers to predict subsequent MRI response as a function of integrated ADC and size change
Evaluate the ability of early ADC change to predict subsequent MRI response
Correlation with % cells +ve for proliferation markers Ki-67 (MIB1), geminin, mcms and tunel apoptosis assay, tumour genotype and mRNA expression markers of proliferation genes in residual tumour (if present).
Determining the causality of each adverse event to the [18F]FLT tracer, and grade AE severity according to NCI CTCAE version 4.0.

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

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

Standard MRI

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.8.4.1

Number of sites anticipated in 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

LPLV

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

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

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)

Standard Care

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

2012-01-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-08-23

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials