Clinical Trials Register

Summary
EudraCT Number:	2005-004001-29
Sponsor's Protocol Code Number:	D8664C00008
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-02-15
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

Czechia - SUKL

A.2

EudraCT number

2005-004001-29

A.3

Full title of the trial

An Open Label, Randomised, Parallel Group, Multicentre Study to
Compare ZOLADEX™ 10.8 mg Given Every 12 Weeks with ZOLADEX
3.6 mg Given Every 4 Weeks in Pre-menopausal Women with Oestrogen
Receptor Positive Advanced Breast Cancer

A.4.1

Sponsor's protocol code number

D8664C00008

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Zoladex LA 10.8 mg implant
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zeneca UK Ltd.
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.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Goserelin
D.3.9.3	Other descriptive name	(as Goserelin acetate)
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	10.8
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Zoladex 3.6 mg Implant
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zeneca UK Ltd.
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.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Goserelin
D.3.9.3	Other descriptive name	(as Goserelin acetate)
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	3.6
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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 receptor (ER) positive advanced breast cancer (ABC) in pre-menopausal women

MedDRA Classification

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 primary objective of this study is to evaluate whether ZOLADEX 10.8 mg is non-inferior to ZOLADEX 3.6 mg in pre-menopausal women with oestrogen receptor (ER) positive advanced breast cancer (ABC) by assessment of progression-free survival (PFS) at 24 weeks.

E.2.2

Secondary objectives of the trial

• To provide supportive data confirming that ZOLADEX 10.8 mg every 12 weeks is
non-inferior to ZOLADEX 3.6 mg every 4 weeks by assessment of:
− Objective response rate (ORR) at 24 weeks, with response defined as complete
or partial response as determined by Response Evaluation Criteria In Solid
Tumours (RECIST) criteria
− Oestradiol (E2) serum concentrations at 24 weeks
• To compare the safety and tolerability profile of ZOLADEX 10.8 mg and
ZOLADEX 3.6 mg by assessment of adverse events (AEs)
• To assess goserelin PK in Japanese and Caucasian patients who have received
ZOLADEX 10.8 mg by assessment of goserelin plasma concentration-time profiles.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetic assessments

E.3

Principal inclusion criteria

Provision of written informed consent
− For the PK analyses in this study (see Section 4.5), optional additional blood
samples will be taken from those patients who provide written informed
consent to confirm that they are willing to participate in this part of the study.
This consent will be in addition to their written informed consent to confirm
their willingness to participate in the main study. See Section 8.3.1 for further
information
2. Female ≥18 years and pre-menopausal
− Pre-menopausal defined as 1) last menses within 1 year of administration of
study drug, and 2) E2 ≥10 pg/mL and FSH ≤30 mIU/mL within 4 weeks of
administration of study drug. For patients who have had a hysterectomy, it is
acceptable to meet only criterion 2.
3. Histological/cytological confirmation of locally advanced or metastatic breast
cancer and are candidates to receive hormonal therapy as therapy for advanced
disease. Patients may have received prior adjuvant chemotherapy, radiotherapy or
hormonal therapy for EBC
4. Documented evidence of hormone sensitivity (ER positive) of primary or secondary
tumour tissue
5. World Health Organization (WHO) Performance status of 0, 1 or 2 (see Appendix D)
6. At least one measurable lesion (not located in a previously irradiated area) according to RECIST with the exception of patients with bone metastases only or complete remission after prior taxane- or anthracycline based first line chemotherapy for ABC (stage IV). See Section 3.3.3, exclusion criterion 4, for further details of eligibility criteria concerning prior first line chemotherapy for ABC.
Patients with bone metastases only must fulfil one of the following conditions:
- Have osteolytic lesions identifiable by bone x-ray (patients with productive bone lesions only, as identified by bone x-ray, are not eligible),
- Have bone lesions identified by MRI or computed tomography scan (patients with productive bone lesions only, as identified by MRI or computed tomography scan, are eligible).
Patients with complete remission after prior taxane- or anthracycline based first line chemotherapy for ABC must fulfil one of the following conditions:
- Have had at least one measurable lesion (not located in a previously irradiated area) according to RECIST prior to taxane- or anthracycline based first line chemotherapy for ABC,
- Have had bone metastases meeting the criteria listed above prior to taxane- or anthracycline based first line chemotherapy for ABC.

E.4

Principal exclusion criteria

1. Patients who have received tamoxifen or other hormonal therapies as adjuvant
therapy for EBC in the 24 weeks before administration of study drug; prior treatment with hormonal therapies for ABC
2. Patients who have received LHRHa as adjuvant therapy for EBC in the 48 weeks
before administration of study drug (up to 2 years of adjuvant treatment with an
LHRHa is permitted)
3. Patients who have received any radiotherapy for EBC or ABC within 4 weeks before administration of study drug
4. Prior first line chemotherapy for ABC with the exception of taxane- or
anthracycline-based chemotherapy providing that a) there is no evidence of
progressive disease since the start of the chemotherapy and b) the patient has
pre-menopausal status after starting chemotherapy. Patients who have had prior
chemotherapy for ABC must have had at least one menstrual period since starting
chemotherapy. Any taxane- or anthracycline-based chemotherapy must be
completed at least 4 weeks prior to Day 1 of this study. (Prior adjuvant
chemotherapy for EBC is allowed except when it has been administered within 4 weeks before study drug administration )
5. Prior treatment with herceptin for EBC within 4 weeks before study drug administration; prior treatment with herceptin for ABC
6. Presence of life-threatening metastatic visceral disease, defined as extensive hepatic
involvement, or any degree (proven or suspected) of brain or leptomeningeal
involvement (past or present) or symptomatic pulmonary lymhangitic spread.
Patients with discrete pulmonary parenchymal metastases are eligible, provided
their respiratory function is not compromised as a result of disease
7. Estimated survival less than 24 weeks from the start of study therapy (Day 1) based on clinical judgment
8. History (within previous 3 years before administration of study drug) of systemic
malignancy other than breast cancer with the exception of basal cell/squamous cell
carcinoma of the skin or cancer of the cervix that has been satisfactorily controlled
9. Platelets <100x109/L; total bilirubin >1.5x upper limit of reference range (ULRR);
alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5xULRR if
no demonstrable liver metastases or >5xULRR in presence of liver metastases
10. Any other significantly abnormal laboratory test result at baseline that would place the patient at unusual risk or confound the results of the study as assessed by the treating investigator
11. Treatment with a non-approved or experimental drug within the preceding 12 weeks before administration of study drug
12. Patients with a relevant history of any severe concomitant disease that would place the patient at unusual risk or confound the results of the study (eg, a strong family history of osteoporosis or severe renal or hepatic impairment) as assessed by the treating investigator
13. Patients who, for whatever reason (eg, confusion, infirmity, alcoholism) are
unlikely to comply with study requirements as assessed by the treating investigator
14. Patients considered by the investigator to be at risk of transmitting any infection
through blood or other body fluids including the agents for acquired immune
deficiency syndrome or other sexually transmitted disease or hepatitis
15. History of bleeding diathesis (ie, disseminated intravascular coagulation or clotting factor deficiency) or long-term anticoagulant therapy (other than antiplatelet
therapy and low dose warfarin)
16. History of any hypersensitivity to active or inactive excipients of ZOLADEX or
tamoxifen
17. Pregnancy or breast feeding
18. Patients unwilling to stop taking any drug known to affect sex hormonal status, or in whom it would be inappropriate to stop
19. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study centre)
20. Previous enrolment or randomisation of treatment in the present study.

E.5 End points

E.5.1

Primary end point(s)

The primary study variable measurement is disease progression. The primary outcome variable is the Progression Free Survival; this is used as the basis for the sample size calculations

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

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.8.3

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.8.5

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

Last patient last visit.

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.1.1.1

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.1.3

Elderly (>=65 years)

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

260

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)

Post study medication is at the discretion of the investigator.

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

2006-02-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-01-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-11-18

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