Clinical Trials Register

Summary
EudraCT Number:	2017-001992-22
Sponsor's Protocol Code Number:	ADVANCE
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:	2018-05-14
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

2017-001992-22

A.3

Full title of the trial

Phase II open label randomised safety and efficacy study of the viral vectored ChAd-MVA 5T4 vaccine in combination with PD-1 checkpoint blockade in low- or intermediate-risk localized or locally advanced prostate cancer and advanced metastatic prostate cancer

A.3.1

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

Novel vaccine against prostate cancer in combination with a drug releasing the brake on the immune system

A.3.2

Name or abbreviated title of the trial where available

VAccination in early and ADvanced prostate caNCEr (ADVANCE)

A.4.1

Sponsor's protocol code number

ADVANCE

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	University of Oxford
B.1.3.4	Country	United Kingdom
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	The European Commission FP7 research grant
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	The Jenner Institute, University of Oxford
B.5.2	Functional name of contact point	Dr Irina Redchenko
B.5.3	Address:
B.5.3.1	Street Address	Old Road Campus Research Building, Roosevelt Drive, Headington
B.5.3.2	Town/ city	Oxford
B.5.3.3	Post code	OX3 7DQ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01865617623
B.5.6	E-mail	irina.redchenko@ndm.ox.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	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.3.1	Product name	ChAdOx1.5T4
D.3.4	Pharmaceutical form	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	ChAdOx1.5T4
D.3.9.3	Other descriptive name	ChAdOx1 virus encoding 5T4 antigen
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.1x10e11
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	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.3.1	Product name	MVA.5T4
D.3.4	Pharmaceutical form	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	MVA.5T4
D.3.9.3	Other descriptive name	MVA virus encoding 5T4 antigen
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1x10e9
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	OPDIVO
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
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.3.1	Product name	OPDIVO
D.3.4	Pharmaceutical form	Solution for infusion
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	Nivolumab
D.3.9.1	CAS number	946414-94-4
D.3.9.3	Other descriptive name	Anti PD-1 antibody
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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

Low- and intermediate-risk prostate cancer and advanced metastatic prostate cancer

E.1.1.1

Medical condition in easily understood language

Early stage and advanced prostate cancer

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10062904
E.1.2	Term	Hormone-refractory prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10066489
E.1.2	Term	Progression of prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10060862
E.1.2	Term	Prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10060862
E.1.2	Term	Prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 assess the safety and efficacy of ChAd-MVA 5T4 vaccination in combination with checkpoint inhibitor nivolumab when administered to early stage and advanced metastatic prostate cancer patients.

E.2.2

Secondary objectives of the trial

1) To assess the magnitude of immune responses generated by ChAd-MVA vaccination in combination with nivolumab.
2) To investigate whether ChAd-MVA vaccination in combination with nivolumab will lead to a change in the composition of immune cell subsets in the prostate.
3) To investigate whether ChAd-MVA vaccinations in combination with nivolumab will impact on prostate cancer progression and overall survival.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Low- or intermediate-risk prostate cancer group:
- Males aged over 18 years
- Histologically confirmed adenocarcinoma of the prostate
- Clinically localised or locally advanced disease deemed operable by the treating consultant urological surgeon i.e.:
• Gleason score ≤ 7
• Local tumour stage ≤T3c and deemed operable
• No evidence of metastases (Nx/N0 and Mx/M0)
• No evidence of high grade Gleason 5 disease
• PSA ≤ 20 ng/ml
- Scheduled for and considered fit for radical prostatectomy
- Absence of any indication to perform urgent surgery that would not allow completion of the study interventions prior to radical prostatectomy

Metastatic prostate cancer groups:
- Males aged over 18 years
- Histologically confirmed adenocarcinoma of the prostate cancer. Note, any Gleason grade or primary tumour staging at diagnosis is permitted.
- Evidence of at least one distant metastasis based on MRI, CT, PET or bone scintigraphy.
- Established on and suitable to continue with androgen deprivation therapy (ADT) using any luteinizing hormone releasing hormone (LHRH) agonist. LHRH agonist therapy may include goserelin (Zoladex®), leuprorelin acetate (Prostap®) or any other licenced product in this class.
- On treatment with anti-androgen therapy using either abiraterone (Zytiga®) or enzalutamide (Xtandi®) and demonstrating evidence of disease progression at the time of enrolment, defined according Prostate Cancer Working Group 2 Criteria as either:
• increasing PSA or;
• progressive nodal or visceral disease or;
• progressive bone metastases
- Suitable to continue therapy with either abiraterone or enzalutamide at the time of enrolment
- Satisfactory functional status defined as Eastern Cooperative Oncology Group (ECOG) Performance Status
≤ 1

E.4

Principal exclusion criteria

All participants:

The patient may not enter the study if any of the following apply:
- Any prior diagnosis or clinical suspicion of autoimmune disease including, but not limited to, systemic lupus erythematosus, inflammatory bowel disease, vasculitis, Grave’s disease and type I diabetes mellitus. Note, subjects with known pre-existing clinically silent positive autoantibodies should not be included.
- Any diagnosis of a non-prostate malignancy within the last 3 years where in the opinion of the investigator the risk of recurrence exceeds 30%
- Participation in another research study involving an investigational product or investigational surgical procedure in the 30 days preceding enrolment, or planned use during the study period
- Any prior exposure to checkpoint inhibitor drugs including anti-PD-1, anti-PD-L1, or anti-CTLA-4 monoclonal antibodies or any prior treatment with investigational vaccines
- History of allergic disease or reaction likely to be exacerbated by any component of the vaccine, e.g. egg products
- Administration of immunoglobulins and/or any blood products within the one month preceding the planned administration of the study drugs
- Seropositive for Hepatitis B (HBV) Hepatitis C virus (HCV), human immunodeficiency virus (HIV)
- Any confirmed or suspected immunocompromised state, including but not limited to, asplenia, a history of atypical, recurrent or severe infections, or, regular use (> 14 days) of systemic immunosuppressant medication within the past 6 months.
- Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema
- History of anaphylaxis in relation to vaccination or any clinically significant allergic disease likely to be exacerbated by any component of the vaccine or checkpoint inhibitor preparations, as listed in the Investigator’s Brochure and SmPC
- Confirmed or suspected recreational drug use or harmful drinking in the last 5 years
- History of a serious psychiatric condition or other circumstances that may be associated with impaired mental capacity
- Other prior malignancy with an estimated ≥ 30% chance of relapse within 2 years. Allowed recent cancers include (but are not limited to) non-melanomatous skin cancer and superficial bladder cancer
- Evidence of significant clinical disorder or laboratory finding which in the opinion of the investigating physician increases the level of risk to the patient, limits the ability of the patient to participate in the study or impairs interpretation of the study data

Exclusion Criteria – Metastatic prostate cancer groups

The volunteer may not enter the metastatic prostate cancer arm of the study if:
- The treating oncologist or urological cancer MDT estimates a subject’s life expectancy to be ≤ 6 months
- Any active, previously treated, or suspected intracranial or leptomeningeal metastases

E.5 End points

E.5.1

Primary end point(s)

1. Actively and passively collected data on adverse events up to 12 months from enrolment

2. Serum PSA kinetics secondary to study treatment as measured by rate of change (low- and intermediate-risk
prostate cancer patients)

3. Reduction of serum PSA and circulating tumor DNA following study treatment (metastatic prostate cancer patients)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Throughout the study, from baseline to last study visit/assessment

2. From baseline to surgery

3. Throughout the study, from baseline to last study visit/assessment

E.5.2

Secondary end point(s)

1. Development or increase of vaccine-specidfic immune response

2. Immune cell subsets in the prostate pre and post study treatment (low- and intermediate-risk
prostate cancer patients)

3. Radiographic progression-free survival (metastatic prostate cancer patients)

4. Overall survival (metastatic prostate cancer patients)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Throughout the study, from baseline to last study visit/assessment

2. 2. From baseline to surgery

3. At 6 and 12 months after enrolment

4. At 6 and 12 months after enrolment

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

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.8.5.1

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

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

Switzerland

United Kingdom

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

The end of the study is three months after the last visit of the last subject to allow for sample analysis.

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