Clinical Trials Register

Summary
EudraCT Number:	2011-005240-10
Sponsor's Protocol Code Number:	C/24/2011
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-02-29
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

2011-005240-10

A.3

Full title of the trial

A phase II, open label, preoperative study to assess the efficacy of the novel steroid sulfatase inhibitor Irosustat in postmenopausal women with early oestrogen receptor positive breast cancer.

A.3.1

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

A study to investigate how a new hormone treatment for breast cancer, called Irosustat, affects the growth of breast cancer.

A.3.2

Name or abbreviated title of the trial where available

IPET version 1.0 27.01.2012

A.4.1

Sponsor's protocol code number

C/24/2011

A.5.4

Other Identifiers

Name:

Ipsen Study Protocol Number

Number:

X-52-58064-011

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	Imperial 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	Imperial Comprehensive Biomedical Research Centre
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Beaufour IPSEN Industrie, Pharmaceutics - CTSU
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Imperial College London
B.5.2	Functional name of contact point	Dr Ioannis Xynos
B.5.3	Address:
B.5.3.1	Street Address	Imperial Clinical Trials Unit – Cancer
B.5.3.2	Town/ city	Imperial College London
B.5.3.3	Post code	W6 8RF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02033115202
B.5.5	Fax number	02087410731
B.5.6	E-mail	i.xynos@imperial.ac.u

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	Irosustat
D.3.2	Product code	BN83495
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Irosustat
D.3.9.1	CAS number	288628-05-7
D.3.9.2	Current sponsor code	Irosustat
D.3.9.3	Other descriptive name	BN83495, also known as STX64 or 667-coumate
D.3.9.4	EV Substance Code	AS1
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	40
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Breast Cancer, ER positive, early

E.1.1.1

Medical condition in easily understood language

Hormone sensitive early Breast Cancer

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10070577
E.1.2	Term	Oestrogen receptor positive 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

This study will use 3’-deoxy-3’-[18F]Fluorothymidine Positron Emission Tomography (FLT-PET) to assess the ability of a novel endocrine treatment for breast cancer, Irosustat, to slow down cancer cell growth.

E.2.2

Secondary objectives of the trial

1) To assess what Irosustat does to the body by measuring blood hormone levels and how much it inhibits its target enzyme activity. 2) To assess safety and tolerability of Irosustat.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Written informed consent to participate in the trial 2) 18 years of age or older 3) Histologically confirmed ER +ve breast cancer (Allred ≥3) 4) Any HER2 status 5) Tumour measuring ≥20mm in longest diameter on ultrasound (US) examination 6)Postmenopausal women as defined by any one of the following criteria: a. Amenorrhoea >12 months at the time of diagnosis and an intact uterus OR, b. prior bilateral oophorectomy OR, c. FSH levels within the postmenopausal range (as per local practice) in women aged <55years who have undergone hysterectomy OR, d. FSH levels within the postmenopausal range (as per local practice) in women aged <55 years who have been on Hormone Replacement Therapy (HRT) within the last 12 months and are therefore not amenorrhoeic 7) Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 8. Adequate bone marrow function defined by Hb≥10 g/dl, WBC≥3.0 x109, PLT≥100 x109/L. Adequate renal function defined by a serum creatinine ≤1.5 x ULN. Adequate liver function defined by total bilirubin ≤ 1.5 ULN (patients with Gilbert’s syndrome exempted), either ALT or AST ≤1.5 ULN and ALP ≤1.5 ULN

E.4

Principal exclusion criteria

1) Locally advanced/inoperable breast cancer 2) Clinical evidence of metastatic disease 3) Diffuse or inflammatory tumours 4) Any history of invasive malignancy within 5 years of starting study treatment (other than adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and cervical carcinoma in situ) 5) Evidence of bleeding diathesis and PTT and PT ≤ 1.5 x upper limit of normal 6) Concomitant use (defined as use within 4 weeks prior to entry) of HRT or any other oestrogen-containing medication or supplement (including vaginal oestrogens and phytoestrogens) 7) Previous use of oestrogen implants at ANY time. 8) Concomitant use of: a) Rifampicin and other CYP2C and 3A inducers such as rifabutin, rifapentine, carbamazepine, phenobarbital, phenytoin and St. John’s Wort b) Systemic carbonic anhydrase inhibitors 9) Any of the following cardiac criteria: a) Mean resting corrected QT interval (QTcf) >450 ms obtained from 3 electrocardiograms (ECGs) b) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval 10) Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels 11) Evidence of uncontrolled active infection 12) Evidence of significant medical condition or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial 13) Subjects unable to lie flat or fit into the scanner 14) Patients on occupational monitoring for radiation exposure

E.5 End points

E.5.1

Primary end point(s)

Changes in FLT uptake as assessed by PET following 2 weeks of treatment with Irosustat.

E.5.1.1

Timepoint(s) of evaluation of this end point

FLT-PET scans will be performed on day 1 and day 14. Every effort must be made to observe the 14 day time point. However, delays of up to 3 days will be acceptable.

E.5.2

Secondary end point(s)

1) To characterize the pharmacodynamic profile of Irosustat by measuring peripheral blood steroid hormone levels and assessing the effect of Irosustat on STS inhibition in PBMCs. 2) To evaluate safety and tolerability of Irosustat by collecting toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03: June 14, 2010).

E.5.2.1

Timepoint(s) of evaluation of this end point

While receiving study treatment patients will attend study visits for clinical evaluation and blood sampling at day 1, day 7, day 14 and at 30 days following the last dose of Irosustat. In addition, patients who have consented to the collection of an optional post treatment tumour sample will attend an additional visit as soon as possible following day 14.

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

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1