Clinical Trials Register

Summary
EudraCT Number:	2007-003240-30
Sponsor's Protocol Code Number:	CR9304-21
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:	2008-06-27
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

2007-003240-30

A.3

Full title of the trial

A Cancer Research UK Phase I/II Open Label Study to Evaluate the Safety, Endocrine Effects, and Anti-tumour Activity of Abiraterone Acetate (CB7630) in Patients with Oestrogen (ER) or Androgen Receptor (AR) Positive Advanced or Metastatic Breast Carcinoma.

A.3.1

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

Phase I/II study of abiraterone in ER or AR positive breast cancer

A.3.2

Name or abbreviated title of the trial where available

Phase I/II study of abiraterone in ER or AR positive breast cancer

A.4.1

Sponsor's protocol code number

CR9304-21

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	Cancer Research UK
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	Johnson & Johnson
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Cancer Research UK
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	Cancer Research UK
B.5.2	Functional name of contact point	Drug Development Office
B.5.3	Address:
B.5.3.1	Street Address	407 St John Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	EC1V 4AD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4402072420200
B.5.5	Fax number	+4402030147633
B.5.6	E-mail	regquery@cancer.org.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Abiraterone Actetate
D.3.2	Product code	CB7630
D.3.4	Pharmaceutical form	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	Abiraterone Acetate
D.3.9.2	Current sponsor code	CB7630
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	250
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

Oestrogen (ER) or androgen receptor (AR) positive, advanced or metastatic breast carcinoma

E.1.1.1

Medical condition in easily understood language

ER or AR positive 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	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
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

Phase I
1. To evaluate the safety and tolerability of abiraterone acetate administered orally continuously in a once-daily regimen in post-menopausal women with advanced breast malignancy.
2. To recommend a trial dose for the Phase II.

Phase II
1. To evaluate the clinical benefit rate in post-menopausal women with ER+ or AR+ER- advanced breast cancer at 24 weeks i.e 6 cycles

E.2.2

Secondary objectives of the trial

Phase I
1. To study abiraterone acetate pharmacokinetics in post-menopausal women.
2. To determine the endocrine impact of abiraterone acetate on the pituitary-adrenal-gonad endocrine axis.
3. To document any anti-tumour activity

Phase II
1. To estimate the duration of objective tumour responses in the two patient cohorts (according to intra-tumoural ER and AR expression).
2. To correlate response rates and duration of response with the endocrine profile (at baseline and brought about by abiraterone acetate).
3. To evaluate two year survival (post Cycle 1 Day 1), after treatment with CB7630 in the two cohorts.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically or cytologically confirmed advanced or metastatic breast carcinoma

2. Evidence of disease progression (off treatment) prior to trial commencement.

3. All patients must have received previous treatment in the adjuvant or metastatic setting:
- ER+ patients must have received at least two types of hormone therapy (e.g. aromatase inhibitors and Tamoxifen)
- HER2+ patients must have received Herceptin plus at least one other line of chemotherapy
- HER - ER- patients must have received at least one line of chemotherapy

4. Post-menopausal defined by:
a) Aged > 60 years or
b) Aged > 45 years with intact uterus and amenorrhoeic for at least 12 months or
c) Aged > 40 years (has not received chemotherapy in the past 12 months) and no menstrual periods for 12 consecutive months (no other biological/physiological cause identified) and hormone levels are consistent with post menopausal status or
d) Aged > 18 years having had a bilateral surgical oopherectomy.

5. Either ER+ (any AR) or AR+ (ER-) disease (by immunohistochemistry)

6. For Phase II only: Measurable disease by RECIST criteria.

7. Life expectancy of at least 3 months.

8. World Health Organisation (WHO) performance status of 0-2.

9. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study.
Lab Test Value required
- Haemoglobin (Hb) ≥9.0 g/dl
- Neutrophils ≥1.5 x 10(9)/L
- Platelets ≥100 x 10(9)/L
- Total bilirubin ≤1.5 x upper normal limit (ULN)
- ALT and AST ≤ 2.5 x ULN (5 x ULN in the presence of liver metastases)
- Creatinine clearance ≥50 ml/min
Or:
Creatinine ≤ 1.5 x ULN

10. Normal potassium and magnesium levels

11. Normal baseline ACTH stimulation test (this will not be required in the Phase II study if no evidence of adrenal insufficiency is observed in the Phase I study).

12. Systolic blood pressure < 160 and diastolic < 95 mmHg documented on at least 3 different
occasions. Hypertension currently under control is permitted.

13. Cardiac Ejection Fraction ≥ 50% measured by MUGA scan/ECHO.

14. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

E.4

Principal exclusion criteria

1. Anti-cancer therapy including radiotherapy (except for palliative reasons), any endocrine
therapy, immunotherapy, chemotherapy, or use of other investigational agents within four
weeks prior to trial entry (six weeks for nitrosureas and Mitomycin-C).

2. ER-and AR- breast cancer by immunohistochemistry

3. Persistent grade 2 or greater toxicities from any cause (Exceptions to this are alopecia or certain Grade 2 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient).

4. Patients with known Central Nervous System (CNS) disease (primary or secondary) or leptomeningeal disease because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events.

5. Gastrointestinal disorders interfering with absorption of the study drug

6. Difficulties with swallowing study capsules

7. Clinical and/or biochemical evidence of hyperaldosteronism or hypopituitarism

8. History of thrombo-embolic disease within 12 months of commencing this trial

9. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies

10. Major thoracic and/or abdominal surgery or significant traumatic injury within 4 weeks prior to trial entry from which the patient has not recovered

11. At high medical risk because of non-malignant systemic disease including active infection or serious concurrent illness

12. Active or uncontrolled autoimmune disease that may require corticosteroid therapy during protocol treatment

13. Known immunocompromised patients, e.g. Human Immunodeficiency Virus (HIV).

14. Current malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.

15. Significant cardiovascular disease as defined by:
a. Congestive heart failure with severity NYHA III or IV (see Appendix 4);
b. History of unstable angina pectoris or myocardial infarction up to 6 months prior to
trial entry;
c. Presence of severe valvular heart disease;
d. Presence of a ventricular arrhythmia requiring treatment.

16. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.

E.5 End points

E.5.1

Primary end point(s)

Phase I
1. Determining causality of each adverse event to abiraterone acetate and grading severity according to NCI CTCAE Version 3.0.

2. The Maximum Tolerated Dose (MTD) or 1000 mg (if MTD is not reached)

Phase II
1. Determining the proportion of patients with stable disease for ≥ 24 weeks or objective response according to RECIST criteria

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout study treatment

E.5.2

Secondary end point(s)

Phase I
a) Plasma levels of abiraterone measured using a validated LC-MS-MS assay.

b) Determining the relationship between dose and endocrine response (and determining the recommended dose for Phase II if MTD is not reached).

c) Disease response as assessed by RECIST criteria

Phase II
a) Determining the duration of objective tumour responses according to RECIST criteria in each cohort.

b) Determining the relationship between tumour and endocrine responses in each cohort.

c) Determining two year survival in each cohort.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

Combined Phase I/II

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

Information not present in EudraCT

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

The ‘end of trial’ is defined as the date when all patients have been followed-up for survival up to 2 years (following the date of first dose) or when all patients have died, according to whichever event occurs first.

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

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

2008-07-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-12-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-04

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