Clinical Trials Register

Summary
EudraCT Number:	2007-003227-20
Sponsor's Protocol Code Number:	D4320C00014
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2007-12-10
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-003227-20

A.3

Full title of the trial

A Phase III, Randomised, Double-blind Study to Assess the Efficacy and
Safety of 10 mg ZD4054 versus Placebo in Patients with Hormone-resistant
Prostate Cancer and Bone Metastasis who are Pain Free or Mildly
Symptomatic

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

D4320C00014

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

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
B.1.3.4	Country	Italy
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	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.3.2	Product code	ZD4054
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ZD4054
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
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Hormone-resistant
Prostate Cancer and Bone Metastasis who are Pain Free or Mildly
Symptomatic

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10036911
E.1.2	Term	Prostate cancer recurrent

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the effect
of ZD4054 on overall
survival, defined as time
to death (from
randomisation) from
any cause, compared to
placebo

E.2.2

Secondary objectives of the trial

1. To assess the effect
of ZD4054 on progression free
survival, defined as time from randomisation into the study until clinical progression of disease,
compared to placebo
2. To investigate the tolerability and safety profile of ZD4054
compared to placebo
3. To assess the effect of ZD4054 on time to use of opiates compared
to placebo
4. To assess the effect of ZD4054 on the
incidence of skeletal related events compared to placebo
5. To investigate the effects of ZD4054 on bone metastases formation compared to
placebo
6. To assess the effects of ZD4054 on Health Related Quality of Life
(HRQOL) compared to placebo
7. To investigate the effect of ZD4054 on time to prostate-specific
antigen (PSA) progression compared
to placebo
8. To assess the effects of ZD4054 on time to pain progression compared to placebo
9. To investigate the effects of ZD4054 on time to initiation of chemotherapy compared to placebo
1o. ......

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

1. Provision of informed consent
2. Male, aged 18 years or older
3. Histological or cytological confirmation of adenocarcinoma of the prostate
4. Documented evidence of bone metastasis on radionuclide bone scan. Patients must
have disease involvement <75% of the spine, pelvis and ribs in the anteroposterior
(AP) or posteroanterior (PA) view. Patients with ≤3 lesions seen on bone scan will
require a CT scan, MRI or x-ray to confirm
5. Biochemical progression of prostate cancer, documented while the patient is
castrate:
− Biochemical progression is defined as at least 2 stepwise increases in PSA over
a period of ≥1 month (values do not need to be consecutive but 2 values that
have increased since the previous highest value are required) with at least
14 days between each measurement irrespective of assay or laboratory
− Historical values may be used
− The last PSA must be an increase of ≥50 % of the first PSA value of the
3 values or an absolute increase of ≥10 ng/mL over the initial PSA
− The final PSA value must be ≥1.2 ng/mL in patients who have had a radical
prostatectomy and ≥5 ng/mL in all other patients
6. Asymptomatic or mild pain from prostate cancer, defined as a score of ≤2 in the
worst pain item of the BPI
7. Surgically castrated or continuously medically castrated with serum testosterone
≤2.4 nmol/L (70 ng/dL)
8. World Health Organisation (WHO) performance status 0 - 1
9. Life expectancy of 6 months or more.

E.4

Principal exclusion criteria

1. Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study
treatment
2. Current use (from the time that written informed consent is given) of any opiates,
with the exception of opiates taken PRN for pain not directly related to prostate
cancer
3. Prior cytotoxic chemotherapy (such as paclitaxel, docetaxel and mitoxantrone) for
the treatment of recurrent prostate cancer (prior estramustine therapy is allowed), as
well as other targeted cancer therapies (such as EGF, EGFR, VEGF and VEGFR)
4. Systemic radionuclide therapy (ie, strontium chloride Sr89, 186Relabeled HEDP, or
153Sm-EDTMP pentasodium) within 12 weeks of starting study treatment
5. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine,
phenobarbitone and St John’s Wort) within 2 weeks of starting study treatment.
Dexamethasone will be allowed if the investigator feels it is necessary but is
encouraged to use a different form of steroid treatment wherever possible
6. Use of systemic retinoids within 2 weeks of starting study treatment
7. Have received investigational drug in another clinical study of anticancer therapy,
within 4 weeks of starting study treatment
8. Prior therapy with endothelin receptor antagonists or family history of
hypersensitivity to endothelin antagonists
9. Neurological symptoms or signs consistent with acute or evolving spinal cord
compression. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously
treated patients are allowed
10. Symptomatic peripheral neuropathy of CTCAE grade 2 or higher
11. Known or suspected central nervous system metastases
12. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
13. Stage II, III or IV cardiac failure (classified according to New York Heart
Association (NYHA) classification) or myocardial infarction within 6 months prior
to study entry
14. QT interval corrected for heart rate eg, by Bazett’s correction >470 msec
15. Previous history or presence of another malignancy, other than prostate cancer or
treated squamous/basal cell carcinoma of the skin, within the last 5 years
16. In the opinion of the investigator, any evidence of severe or uncontrolled systemic
disease (eg, currently unstable or uncompensated respiratory, cardiac, hepatic or
renal disease) or evidence of any other significant clinical disorder or laboratory
finding that makes it undesirable for the patient to participate in the study
17. Hemoglobin (Hb) <9 g/dL. Concomitant use of erythropoietin or blood
transfusions is allowed
18. Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to
patients with Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of evidence of haemolysis or hepatic
pathology), who will be allowed in consultation with their physician
19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times
the ULN or 5 times the ULN in the presence of liver metastasis
20. Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault
equation or by 24-hour creatinine clearance
21. ......

E.5 End points

E.5.1

Primary end point(s)

Overall survival defined as:
Time to death (from randomisation) from any cause

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

Yes

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Information not present in EudraCT

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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.8.6 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

Information not present in EudraCT

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	No
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	18
F.4.2	For a multinational trial
F.4.2.1	In the EEA	295
F.4.2.2	In the whole clinical trial	580

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

2007-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-11-08

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2011-06-30

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