Clinical Trials Register

Summary
EudraCT Number:	2014-000273-39
Sponsor's Protocol Code Number:
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-07-20
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

2014-000273-39

A.3

Full title of the trial

Neo-adjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and RADium-223 for new presentation T1-4 N0/1 M1B adenocarcinoma of prostate (ADRRAD Trial)

A.3.1

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

Trial investigating hormone injections, external beam radiotherapy and intravenous radionuclide injection in patients with advanced prostate cancer.

A.3.2

Name or abbreviated title of the trial where available

ADRRAD

A.4.1

Sponsor's protocol code number

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	Belfast Health and Social Care Trust
B.1.3.4	Country
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	Bayer PLC
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	Belfast Health and Social Care Trust
B.5.2	Functional name of contact point	Prof Joe O'Sullivan
B.5.3	Address:
B.5.3.1	Street Address	Centre for Cancer Research and Cell Biology
B.5.3.2	Town/ city	97 Lisburn Road
B.5.3.3	Post code	BT97AE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	07786652942
B.5.6	E-mail	joe.osullivan@qub.ac.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	Yes
D.2.1.1.1	Trade name	Xofigo 1000 kBq/mL solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
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	Radium 223 dichloride
D.3.9.1	CAS number	444811-40-9
D.3.9.3	Other descriptive name	Xofigo
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	kBq/ml kilobecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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	Yes
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.IMP: 2
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 3.6mg implant
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, UK.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	No
D.3.7	Routes of administration for this IMP	Implantation
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Goserelin acetate ATC=L02AE03
D.3.9.1	CAS number	145781-92-6
D.3.9.4	EV Substance Code	AS3
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)	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.IMP: 3
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 10.8mg implant
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, UK.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	No
D.3.7	Routes of administration for this IMP	Implantation
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Goserelin acetate ATC=L02AE03
D.3.9.1	CAS number	145781-92-6
D.3.9.4	EV Substance Code	AS2
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)	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.IMP: 4
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	Prostap SR DCS
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda UK Limited Building 3, Glory Park, Glory Park Avenue, Wooburn Green, BUCKS, HP10 0DF, UK
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Intramuscular use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	leuprorelin acetate ATC = L02AE02
D.3.9.1	CAS number	74381-53-6
D.3.9.4	EV Substance Code	AS4
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	3.75
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.IMP: 5
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	Prostap 3 DCS
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda UK Limited Building 3, Glory Park, Glory Park Avenue, Wooburn Green, BUCKS, HP10 0DF, UK
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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 suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	leuprorelin acetate ATC = L02AE02
D.3.9.1	CAS number	74381-53-6
D.3.9.4	EV Substance Code	AS5
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	11.25
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.IMP: 6
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	Decapeptyl SR 3mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Ipsen Limited 190 Bath Road Slough Berkshire SL1 3XE United Kingdom
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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 for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Triptorelin Acetate ATC = L02AE04
D.3.9.1	CAS number	57773-63-4
D.3.9.4	EV Substance Code	AS6
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
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.IMP: 7
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	Decapeptyl SR 11.25mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Ipsen Limited 190 Bath Road Slough Berkshire SL1 3XE United Kingdom
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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 for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Triptorelin Acetate ATC = L02AE04
D.3.9.1	CAS number	57773-63-4
D.3.9.4	EV Substance Code	AS7
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	11.25
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic castration sensitive prostate cancer

E.1.1.1

Medical condition in easily understood language

Advanced prostate cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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

In early metastatic prostate cancer is it feasible to deliver LHRH agonist therapy alongside external radiotherapy to prostate gland and pelvic lymph nodes and alongside intravenous radionuclide (Radium223) treatment without undue toxicity?

E.2.2

Secondary objectives of the trial

What effect does treatment as outlined in A10 have on blood markers of disease (PSA and ALP)?
What effect does treatment as outlined in A10 have on disease as seen on radiographic studies (MRI)?
What effect does treatment as outlined in A10 have on time to develop first Symptomatic Skeletal Event (SSE – defined as any of: first use of external beam radiotherapy to relieve skeletal symptoms; new symptomatic pathological vertebral or non-vertebral bone fracture; spinal cord compression; tumour-related orthopaedic surgical intervention.)
What effect does treatment as outlined in A10 have on tumour cells detectable in blood?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent obtained prior to any study-related procedures
2. Histologically confirmed prostate cancer stage T1-4 N0-1, M1b
3. Patients with ≥3 bone metastases showing uptake at bone scintigraphy
4. WHO performance status 0 or 1.
5. Life expectancy of at least 12 months.
6. Age ≥ 18years.
7. Absolute neutrophil count (ANC) ≥ 1.5 x109/L
8. Platelet count ≥ 100 x109/L
9. Hemoglobin ≥10.0 g/dL (100 g/L; 6.2 mmol/L)
10. Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
11. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
12. Creatinine ≤ 1.5 x ULN
13. Albumin > 25 g/L
14. Patients, even if surgically sterilized (i.e. status post-vasectomy), who:
- will abstain from intercourse
- or must agree to use barrier contraception during and for 6 months after discontinuation of study treatment. If patient impregnates a woman while on treatment or within 3 months of discontinuing treatment, he should inform his treating physician immediately.
15. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
16. Willing and able to comply with the protocol, including follow-up visits and examinations

E.4

Principal exclusion criteria

1. Active uncontrolled bacterial, viral or fungal infection.
2. History of another malignancy within the last five years except adequately treated basal cell carcinoma of skin.
3. History of organ allografts requiring immunosuppressive therapy.
4. Serious uncontrolled concomitant disease.
5. Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period or follow-up
6. Received previous radiotherapy to > 25% of bone marrow, including hemibody radiation
7. Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium-223 chloride) for the treatment of bony metastases
8. Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) (or other imaging modality)
9. Imminent or history of spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI)
10. Any other serious illness or medical condition, such as but not limited to:
i) Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2
ii) Cardiac failure New York Heart Association (NYHA) III or IV
iii) Crohn’s disease or ulcerative colitis
iv) Bone marrow dysplasia
v) Faecal incontinence
vi) History of diverticulitis
11. Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
12. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study entry or during the study]

E.5 End points

E.5.1

Primary end point(s)

Toxicity associated with concurrent treatment with LHRH agonist (hormone) injections, external beam radiotherapy to pelvis and intravenous Radium223 dichloride.

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will be clinically assessed and complete EPIC radiotherapy toxicity assessment weekly during radiotherapy, then four weekly during Radium223 treatment phase. They will then be clinically assessed and complete EPIC radiotherapy toxicity assessment 8 weeks following last Radium223 injection and again at end of study.

E.5.2

Secondary end point(s)

What effect does treatment as outlined in A10 have on blood markers of disease?
What effect does treatment as outlined in A10 have on disease as seen on radiographic studies (MRI)?
What effect does treatment as outlined in A10 have on tumour cells detectable in blood?
What effect does treatment as outlined in A10 have on time to develop first Symptomatic Skeletal Event (SSE – defined as any of: first use of external beam radiotherapy to relieve skeletal symptoms; new symptomatic pathological vertebral or non-vertebral bone fracture; spinal cord compression; tumour-related orthopaedic surgical intervention.)

E.5.2.1

Timepoint(s) of evaluation of this end point

Blood markers of disease will be checked at baseline and prior to each cycle of Radium223 treatment (four weekly for six cycles in total). They will be checked again 8 weeks post last injection of Radium223 and again at end of study.

Whole body MRI and bone scan will be performed at baseline and again 8 weeks following final injection of Radium223 and again at end of study.

Peripheral blood will be checked for circulating tumour cells at baseline and prior to each cycle of Radium223 treatment (four weekly for six cycles in total). It will be checked again 8 weeks post last injection of Radium223 and again at end of study.

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

Yes

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

Database lock (effectively LVLS).

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