Clinical Trials Register

Summary
EudraCT Number:	2009-014446-28
Sponsor's Protocol Code Number:	JANUS
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2009-12-14
Trial 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

2009-014446-28

A.3

Full title of the trial

A PHASE II TRANSLATIONAL STUDY INVESTIGATING THE BIOLOGICAL EFFECTS OF THE ZOLEDRONIC ACID AS NEOADJUVANT THERAPY ON INVASIVE PROSTATE CANCER

A.3.2

Name or abbreviated title of the trial where available

THE JANUS TRIAL

A.4.1

Sponsor's protocol code number

JANUS

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	UNIVERSITA` CAMPUS BIOMEDICO
B.1.3.4	Country	Italy
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
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	ZOMETA*IV 1FL 4MG+1F 5ML SOLV
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Zoledronic acid
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	4
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	Yes
D.3.11.13.1	Other medicinal product type	chimico

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

invasive prostate cancer

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10036917
E.1.2	Term	Prostate cancer stage I

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 whether the infusion of zoledronic acid in neoadjuvant setting causes an increase in apoptotic markers between baseline and surgery, both at serum and tissue levels

E.2.2

Secondary objectives of the trial

"To determine whether the infusion of zoledronic acid in neoadjuvant setting causes an increase in angiogenic markers To determine whether the infusion of zoledronic acid in neoadjuvant setting causes a decrease of proliferation markers between baseline and surgery,at tissue levels(ki-67)To detect the presence of circulating tumour cells(CTCs),endothelial circulating cells(CECs)and endothelial progenitor cells(CEPs)in the peripheral blood and the presence of disseminated tumor cells(DTCs)in the bone marrow and changes in response to zoledronic acid To measure bone markers(BALP(serum),CTX(serum)and NTX(urine))at time 0,at every zoledronic acid infusion and prior to surgery To measure PSA serum levels at time 0,at every zoledronic acid infusion and prior to surgery To detect the presence of T cell subsets in the peripheral blood(taken at time 0,at every zoledronic acid infusion and prior to surgery)and changes in response to trea"

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Men with histological diagnosis of prostate cancer
Stage T1c or T2a disease AND PSA value of 10 ng/ml or less AND a Gleason score of 6 or less
Men older than 75 years OR life expectancy of less than 10 years: PSA can be greater than 10 ng/ml OR the Gleason score can be 7 (3 + 4)
Age ≥ 18 years
WHO performance status 0-2
Written informed consent to all required assessments
Patients must have undergone a core biopsy for the diagnosis of their prostate cancer

E.4

Principal exclusion criteria

T0, T1a,b, T2b,c, T3 tumours AND/OR Gleason > 7 AND/OR PSA > 10 if life expectancy > 10 years
Previous hormone or radiotherapy to the treated prostate
Evidence of metastatic disease or recurrent prostate cancer
Previous diagnosis of malignancy unless
o non-melanomatous skin cancer
Serum creatinine > 1.5 x upper limit of normal reference range or calculated creatinine clearance <40 mls/min
Prior treatment with bisphosphonates in the last year
Requiring anticoagulation with warfarin or coumarin derivatives
Known hypersensitivity to bisphosphonates
Current active dental problems including dental abcess or infection of the jawbone (maxilla or mandible) or a current or prior diagnosis of osteonecrosis of the jaw
Recent (within 4 weeks) or planned dental or jaw surgery (recent dental fillings, teeth scaling, polishing or minor gingival surgery do not exclude the patient)
History of bone metabolism diseases
History of active acute and/or chronic inflammatory diseases
Fever (> 37.5 C) in the two weeks before the study enter
Concomitant prolonged treatment with steroids (either IV or oral)

E.5 End points

E.5.1

Primary end point(s)

Increase in apoptotic following zoledronic acid infusion in neoadjuvant setting

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

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Con lesecuzione dellintervento chirurgico finisce la fase di studio e Lei ricevera` le terapie che i suoi medici curanti riterranno piu` adeguate e sara` seguito come di norma.

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	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
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	33

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

2009-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-07-21

P. End of Trial
P.	End of Trial Status	Ongoing

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