Clinical Trials Register

Summary
EudraCT Number:	2012-000101-69
Sponsor's Protocol Code Number:	EGD-EC-005
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-07-04
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

Netherlands - Competent Authority

A.2

EudraCT number

2012-000101-69

A.3

Full title of the trial

An exploratory, open label, single-arm study to evaluate the effect of Eligard® 6-month on biomarkers of disease in patients with metastatic prostate cancer.

Een verkennend, open-label, enkel-arm onderzoek om het effect van Eligard®-6 maanden op ziekte-biomarkers bij patiënten met gemetastaseerde prostaatkanker te beoordelen.

A.3.1

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

A study in patients with metastatic prostate cancer to assess how the drug Eligard®, affects certain markers in blood and urine, which are indicators for the disease.

Een onderzoek in patiënten met uitgezaaid prostaatkanker om te bepalen hoe het geneesmiddel Eligard®, bepaalde markers in bloed en urine, die indicatief zijn voor de ziekte, beinvloedt.

A.3.2

Name or abbreviated title of the trial where available

EFFECT study

EFFECT studie

A.4.1

Sponsor's protocol code number

EGD-EC-005

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	Astellas Pharma Europe Ltd. (APEL)
B.1.3.4	Country	United Kingdom
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	Astellas Pharma Europe Ltd. (APEL)
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	Global Development Operations
B.5.2	Functional name of contact point	Service Desk
B.5.3	Address:
B.5.3.1	Street Address	Sylviusweg 62
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 BE
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031715455878
B.5.5	Fax number	0031715455224
B.5.6	E-mail	contact@nl.astellas.com

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	Eligard 45 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
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

Patients with metastatic prostate cancer whom androgen deprivation therapy (ADT) is indicated

Patiënten met gemetastaseerde prostaatkanker voor wie androgeen deprivatie therapie (ADT) wordt voorgeschreven.

E.1.1.1

Medical condition in easily understood language

Patients with metastatic prostate cancer

Patiënten met gemetastaseerde prostaatkanker

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10007113
E.1.2	Term	Cancer of prostate
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

To explore the effect of Eligard® on the following prostate cancer biomarkers:
• Testosterone in serum
• Prostate Specific Antigen (PSA) in serum
• Prostate Cancer Antigen (PCA3) in urine
• PSA mRNA in blood/PBMC
• PCA3 mRNA in blood/PBMC
• TMPRSS2-ERG mRNA in blood/PBMC

A blood sample for RNA analysis will also be collected and stored for future investigation in patients who have given informed consent for these samples to be collected.

Om het effect van Eligard® op de volgende prostaatkanker biomarkers te onderzoeken:
- Testosteron in serum
- Prostaat Specifiek Antigeen (PSA) in serum
- Prostaat Kanker Antigeen (PCA3 score) in urine
- PSA mRNA in bloed/PBMC
- PCA3 mRNA in bloed/PBMC
- TMPRSS2-ERG mRNA in bloed/PBMC

Een bloedmonster voor toekomstig RNA analyse zal worden afgenomen en opgeslagen van patiënten die daar een apart informed consent voor geven.

E.2.2

Secondary objectives of the trial

Not applicable

Niet van toepassing

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male aged 18 years or older.
2. Confirmed metastatic prostate cancer for whom androgen deprivation therapy (ADT) is indicated.
3. Non-castrate level of serum testosterone (≥ 8 nmol/L (i.e.230 ng/dL)) at screening.
4. Serum PSA ≥ 5 ng/mL at screening.
5. Eastern Cooperative Oncology Group (ECOG) score of 0-2
6. A life expectancy of at least 12 months.
7. Is able to tolerate injections of study drug and comply with the study requirements.
8. Positive blood PSA mRNA at screening. A positive PSA mRNA in PBMCs (defined as exceeding the Limit of Detection for the central lab assay, i.e. ≥ 10 copies per PCR).
9. Patient has given written informed consent

1. Man van 18 jaar of ouder.
2. Bevestigde uitgezaaide prostaatkanker voor wie androgeen deprivatie therapie (ADT) wordt voorgeschreven.
3. Niet-castratie niveau van serum testosteron (≥ 8 nmol/L (i.e. 230 ng/dL)) bij screening.
4. Serum PSA ≥ 5 ng/mL bij screening.
5. Eastern Cooperative Oncology Group (ECOG) score van 0-2.
6. Een levensverwachting van tenminste 12 maanden.
7. Is in staat om injecties van het bestudeerde geneesmiddel te tolereren en te voldoen aan de studie eisen.
8. Positief PSA mRNA in bloed bij screening. Een positief PSA mRNA in PBMCs (gedefinieerd als signaal > Limit of Detection van de centrale labtest i.e. ≥ 10 kopieën per PCR).
9. Patiënt heeft schriftelijk toestemming gegeven (informed consent).

E.4

Principal exclusion criteria

1. History of bilateral orchidectomy.
2. History of any hormonal treatment/therapy with GnRH agonist, GnRH anti-agonist within 6 months of enrolment.
3. Treatment with anti-androgens (except where used to prevent testosterone flare up, starting up to 2 weeks prior to Eligard injection, according to local treatment guidelines), 5-α reductase inhibitors, estrogens and/or other any investigational hormone-derivative within 3 months of enrolment or 5-times the half-life, whichever is longer.
4. Any previous treatment with chemotherapy treatment for prostate cancer prior to the screening visit or within 6 months prior to screening for any other cancer.
5. Patients previously treated for cancer with hormonal therapy in whom treatment was stopped due to lack of efficacy, progression of the disease or lack of tolerability.
6. Previous treatments for cancer (including prostate cancer) within 6 months prior to enrolment: immunotherapy, external beam radiotherapy, brachytherapy, thermotherapy, or biological response modifiers (e.g. cytokines).
7. Known or suspected spinal cord compression or evidence of spinal metastases with risk of spinal compression,
8. Uni- or bilateral uretric obstruction.
9. Requiring concomitant use of anti-androgens during the course of the study (except where used to prevent testosterone flare up, starting up to 2 weeks prior to Eligard injection and continuing for up to 3 weeks, according to local treatment guidelines).
10. Previous or concomitant malignancies at other sites except effectively treated non-melanoma skin cancer or an effectively treated malignancy that has been in remission for at least 5 years.
11. Major surgery within 2 months prior to enrolment.
12. Absolute neutrophil count < 1,500/μL, platelet count < 100,000/μL, and hemoglobin < 5.6 mmol/L (9 g/dL) at screening.
13. Total bilirubin > 1.5 times the upper limit of normal (ULN) at screening. This will not apply to subjects with Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with the sponsor.
14. Alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) > 2 times ULN at screening.
15. Creatinine > 177 μmol/L (2 mg/dL) at screening.
16. Albumin ≤ 30 g/L (3.0 g/dL) at screening.
17. Any clinical condition, diagnosis, symptomatology or ongoing investigation, which, in the opinion of the Investigator, contraindicates their participation in this study.
18. Participation in any clinical study within ≤ 1 month prior to screening (or 5 half lives of the drugs under investigation, whichever is greater).
19. Not available for follow-up assessments or unable to comply with study requirements.
20. Known or suspected hypersensitivity to leuprorelin acetate, to other GnRH agonist or to
any of the excipients of Eligard.
21. Male subjects who are intending to donate sperm within 9 months following the injection of Eligard
22. Male subjects and their female spouses/partners who are of childbearing potential and
are NOT using highly effective contraception consisting of two forms of birth control
(one of which must be a barrier method) starting at Screening and continuing for
9 months from the time of the Eligard injection. Acceptable forms include:
i. Established use of oral, injected or implanted hormonal methods of contraception.
ii. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
iii.Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

1. Voorgeschiedenis van bilaterale orchidectomie.
2. Voorgeschiedenis van hormonale behandeling/therapie met een GnRH-agonist, GnRH anti-agonist binnen 6 maanden voor insluiting.
3. Behandeling met anti-androgenen (behalve wanneer dit dient om een testosteron flare te voorkomen en er tot 2 weken voor de Eligard injectie mee wordt gestart, volgens lokale richtlijnen) , 5-α-reductaseremmers, oestrogenen en/of elk experimentele hormonale derivaat binnen 3 maanden voor insluiting of 5 maal de halfwaardetijd, welke het langste is.
4. Een eerdere behandeling met chemotherapie voor prostaatkanker voorafgaand aan het screeningsbezoek of binnen 6 maanden voorafgaand aan de screening voor elke andere vorm van kanker.
5. Patiënten die eerder behandeld zijn voor kanker met hormonale therapie bij wie de behandeling werd gestopt wegens gebrek aan werkzaamheid, progressie van de ziekte of gebrek aan verdraagzaamheid.
6. Eerdere behandelingen voor kanker (met inbegrip van prostaatkanker) binnen 6 maanden voorafgaand aan de insluiting: immunotherapie, uitwendige bestraling, brachytherapie, thermotherapie of biologische response modifiers (bijvoorbeeld cytokines).
7. Bekende of verdachte compressie van het ruggenmerg of tekenen van spinale metastasen met het risico van compressie van het ruggenmerg.
8. Uni- of bilaterale urineweg obstructie.
9. Noodzaak van gelijktijdig gebruik van anti-androgenen tijdens de studie (behalve wanneer dit dient om een testosteron flare te voorkomen, er tot twee weken voor de Eligard injectie mee wordt gestart en tot 3 weken wordt voortgezet, volgens lokale richtlijnen).
10. Eerdere of huidige andere maligniteiten, behalve effectief behandelde non-melanoom huidkanker of een effectief behandelde maligniteit die in remissie is gedurende tenminste 5 jaar.
11. Een grote operatie binnen 2 maanden voorafgaand aan de insluiting.
12. Absoluut aantal neutrofielen (ANC) < 1.500/μL, aantal trombocyten < 100.000/μL, en hemoglobine < 5.6 mmol/L (9 g/dL) bij de screening.
13. Totaal bilirubine > 1.5 keer de bovengrens van de normaal waarde (ULN) bij screening. Dit zal niet van toepassing zijn op proefpersonen met het syndroom van Gilbert (aanhoudende of terugkerende hyperbilirubinemie die voornamelijk ongeconjugeerd is in de afwezigheid van bewijs voor hemolyse of lever pathologie), wie worden toegestaan in overleg met de sponsor.
14. Alanine aminotransferase (ALAT) of aspartaat aminotransferase (ASAT) > 2 maal de ULN bij de screening.
15. Creatinine > 177 μml/L (2 mg/dL) bij screening.
16. Albumine ≤ 30 g/L (3.0 g/dL) bij screening.
17. Elke klinische conditie, diagnose, symptomen of lopend onderzoek, dat, naar het oordeel van de onderzoeker, een contra-indicatie vormt voor hun deelname aan deze studie.
18. Deelname aan een klinische studie binnen 1 maand voorafgaand aan de screening (of 5 maal de halfwaardetijd van de onderzochte geneesmiddelen, welke groter is.
19. Niet beschikbaar voor follow-up bezoeken/evaluaties of niet in staat om te voldoen aan de onderzoekseisen.
20. Bekende of vermoede overgevoeligheid voor leuprorelineacetaat, andere GnRH agonisten of een van de hulpstoffen van Eligard.
21. Mannelijke proefpersonen die van plan zijn om sperma te doneren binnen 9 maanden na de injectie van Eligard.
22. Mannelijke proefpersonen en hun vrouwelijke echtgenoten/partners die in de vruchtbare leeftijd zijn en GEEN gebruik maken van een zeer effectieve anticonceptie methode, bestaande uit twee vormen van anticonceptie (waarvan er één een barrière methode moet zijn) vanaf screening en voortgezet gedurende 9 maanden vanaf het moment van de Eligard injectie. Aanvaardbare vormen omvatten:
i. Langdurig gebruik van orale, ingespoten of ingebrachte hormonale anticonceptie methoden.
ii. Het plaatsen van een spiraaltje (IUD) of intra-uterien systeem (IUS).
iii. Barrière anticonceptie methoden: condoom of occlusieve cap (diafragma of cervicale/afsluiting caps) met zaaddodend schuim/gel/film/crème/zetpil.

E.5 End points

E.5.1

Primary end point(s)

Biomarker: Changes from baseline of the following biomarker variables:

● Testosterone levels in serum
● PSA level in serum
● PCA3 score in urine
● Number of PSA mRNA copies in blood/PBMC
● Number of PCA3 mRNA copies in blood/PBMC
● Number of TMPRSS2-ERG mRNA copies in blood/PBMC

Safety: Reported treatment-emergent adverse events, including the grading according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.3).

Biomarker: verandering ten opzichte van baseline van de volgende biomarker variabelen:

- Testosteron levels in serum
- PSA level in serum
- PCA3 score in urine
- Aantal PSA mRNA kopieën in bloed/PBMC
- Aantal PCA3 mRNA kopieën in bloed/PBMC
- Aantal TMPRSS2-ERG mRNA kopieën in bloed/PBMC

Veiligheid:
Gerapporteerde bijwerkingen (gestart na behandeling met Eligard), inclusief de gradering volgens de gemeenschappelijke terminologie Criteria voor Adverse Events (CTCAE), versie 4.0.3.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 24 weeks.

Tot en met 24 weken.

E.5.2

Secondary end point(s)

Not applicable.

Niet van toepassing.

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable.

Niet van toepassing.

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

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

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Exploratory Biomarkers

Verkennende biomarkers.

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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

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

End trial will be when the last subject has completed last visit at week 24;

Or

When the sponsor is aware of information on matters concerning the quality, efficacy, and safety of the study drugs, as well as other important information that may affect proper conduct of the clinical study, the sponsor may discontinue the clinical study and send a written notice of the discontinuation along with the reasons to the investigator.

Het einde van het onderzoek zal zijn wanneer de laatste patiënt zijn laatste bezoek in week 24 heeft voltooid.

Of

Als de sponsor op de hoogte is van informatie over zaken met betrekking tot de kwaliteit, de effectiviteit, en de veiligheid van de studiemedicatie, of andere belangrijke informatie dat een goed verloop van het klinisch onderzoek kan beïnvloeden, mag de sponsor het klinisch onderzoek beëindigen en zal de onderzoeker schriftelijk op de hoogte brengen hiervan met de redenen.

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

F.2.2

Male

Yes

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.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)

None.

Geen.

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

2013-07-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-03

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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