Clinical Trials Register

Summary
EudraCT Number:	2009-016217-23
Sponsor's Protocol Code Number:	CA184-095
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-09-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2009-016217-23

A.3

Full title of the trial

Randomized, Double-Blind, Phase 3 Trial to Compare the Efficacy of Ipilimumab vs Placebo in Asymptomatic or Minimally Symptomatic Patients with Metastatic Chemotherapy-Naïve Castration Resistant Prostate Cancer

Revised Protocol Number 03 incorporating Amendment 08
+ Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific (version 3.0 dated 11-Jan-10)
+ Immune Monitoring Amendment 04 (version 1.0 dated 18-Mar-11)-Site Specific
+ Protocol Amendment 07 - Site Specific (version 1.0 dated 02-Jan-14)

A.3.1

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

Study of immunotherapy to treat advanced prostate cancer

A.4.1

Sponsor's protocol code number

CA184-095

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01057810

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	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation
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	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GCT-SU
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.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	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	Ipilimumab
D.3.2	Product code	BMS-734016 / MDX010
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	IPILIMUMAB
D.3.9.1	CAS number	477202-00-9
D.3.9.2	Current sponsor code	BMS-734016 / MDX010
D.3.9.3	Other descriptive name	IPILIMUMAB
D.3.9.4	EV Substance Code	SUB29397
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	50
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)	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	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.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	Ipilimumab
D.3.2	Product code	BMS-734016 / MDX010
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	IPILIMUMAB
D.3.9.1	CAS number	477202-00-9
D.3.9.2	Current sponsor code	BMS-734016 / MDX010
D.3.9.3	Other descriptive name	IPILIMUMAB
D.3.9.4	EV Substance Code	SUB29397
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	200
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)	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
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Castration Resistant Prostate Cancer

E.1.1.1

Medical condition in easily understood language

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
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 compare overall survival of subjects with chemotherapy-naïve Castration Resistant Prostate Cancer (CRPC) who have been randomized to ipilimumab vs placebo.

E.2.2

Secondary objectives of the trial

• Compare Progression Free Survival (PFS)
• Compare time to subsequent non-hormonal systemic therapy
• Compare time to pain progression

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Immune Monitoring Amendment Number 04 - Site Specific (version 1.0
dated 18-Mar-11):
The purpose of this amendment is to permit the collection of blood
(serum) samples for use in exploratory research studies or to test
previously identified potential biomarkers of immunotherapy efficacy or
toxicity. BMS will use biomarkers obtained from the samples and health
information collected from the main clinical trial, CA184095 case report
form, to search for associations between serum biomarkers such as but
not limited to: CRP, cytokines, NKG2D ligands, and anti-tumor antibodies as biomarkers of ipilimumab efficacy. Samples from this and other clinical studies may also be used together to accomplish this objective.

E.3

Principal inclusion criteria

1) Signed Written Informed Consent

2) Target Population
a) Histologic or cytologic confirmation of adenocarcinoma of the prostate;
b) Have been treated by orchiectomy or are receiving a LH-RH analog, and have a
testosterone level  50 ng/dL;
c) Metastatic disease by any 1 of the following modalities: CT, MRI, bone scan;
d) Progression during hormonal treatment. For eligibility purposes, progressive
disease is defined as:
i) Rising PSA values at a minimum of 1-week intervals and a 2.0 ng/mL
minimum starting value OR;
ii) Progression per bone scan: the appearance of 2 or more new lesions, OR;
iii) Progression per target lesions/measurable disease: nodal progression, per
modified RECIST 1.0. Only lymph nodes greater than 2 cm will be considered
to assess a change in size qualifying for disease progression.
e) Anti-androgens (bicalutamide, flutamide, nilutamide) or adrenal androgen
production inhibitors (aminoglutethamide or ketoconazole) should be
discontinued prior to starting study therapy:
i) Subjects with a history of response to an anti-androgen or adrenal androgen
production inhibitor and subsequent progression while on that anti-androgen
should be assessed for anti-androgen withdrawal response for 4 weeks, and
must demonstrate progression, as described in Inclusion Criterion 2) d), off
anti-androgen prior to enrollment;
ii) For subjects that have never responded to anti-androgens, observation for
anti-androgen withdrawal response is not necessary; however, a 2 week
washout period is required prior to start of study therapy
f) ECOG Performance Status 0-1;
g) Asymptomatic or minimally symptomatic.
i) Minimally symptomatic disease will be defined as the following:
(1) If cancer related pain is present, the pain must be rated by the patient as
≤4 according to item #3 of the BPI-SF (“[on a scale of 0 to 10]...describe
your pain at its worst in the last 24 hours.”) for all days during the 5 day
assessment period prior to randomization;
(2) Any cancer related pain must not require any opiate analgesics (including
codeine and dextropropoxyphene) over the 5 day assessment period prior
to randomization.

3) Age and Sex
a) Men ≥18 years of age or minimum age of consent per local regulations.

E.4

Principal exclusion criteria

1) Sex and Reproductive Status
a) Sexually active fertile men not using effective birth control if their partners are
women of childbearing potential (WOCBP).
2) Target Disease
a) Visceral (liver, lung or brain) metastases are not permitted;
3) Medical History and Concurrent Diseases
a) Autoimmune disease: subjects with a documented history of inflammatory bowel
disease, including ulcerative colitis and Crohn’s disease are excluded from this
study. Subjects with a history of symptomatic disease (eg, rheumatoid arthritis,
autoimmune thyroiditis (eg, Hashimoto’s disease), autoimmune hepatitis,
systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus,
autoimmune vasculitis (eg, Wegener’s Granulomatosis); Subjects with motor
neuropathy considered of autoimmune origin (eg, Guillain-Barré Syndrome) are
excluded from this study. Patients with vitiligo are eligible to enter the study.
b) Less than 1 year since resolution of ≥ Grade 2 toxicity related to pelvic-targeted
therapy (eg, radiation enteritis);
c) Dementia, altered mental status, or any psychiatric condition that would prohibit
the understanding or rendering of informed consent or completing questionnaires;
d) A serious uncontrolled medical disorder that, in the opinion of the investigator,
would impair the ability of the subject to receive protocol therapy;
e) Prior malignancy active within the previous 3 years except for locally curable
cancers that have been apparently cured and needing no subsequent therapy, such
as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in
situ of the breast;
f) Known HIV or Hepatitis B or Hepatitis C infection, based on testing performed
during the CA184095 screening period.
4) Physical and Laboratory Test Findings
a) Inadequate hematologic function defined by an absolute neutrophil count (ANC)
< 1,500/mm3, a platelet count < 100,000/mm3, or a hemoglobin level < 9 g/dL;
b) Inadequate hepatic function defined by a total bilirubin level ≥ 2.5 times the upper
limit of normal (ULN), AST and ALT levels ≥ 2.5 times the ULN;
c) Inadequate renal function defined by a serum creatinine level ≥ 2.5 times the
ULN;
d) Inadequate creatinine clearance defined as less than 50 mL/min;
5) Prohibited Treatments and/or Therapies
a) Prior treatment with any immunotherapy for prostate cancer, including autologous
prostate cancer vaccine sipuleucel-T (Provenge®);
b) Prior or ongoing cytotoxic therapy for metastatic prostate cancer (eg, docetaxel,
mitoxantrone, estramustine);
c) Pelvic-targeted radiotherapy within 3 months prior to the start of study therapy.
Bone-directed radiotherapy for palliation of painful bone metastases to pelvic
region is allowed;
d) Chronic use of immunosuppressants and/or systemic corticosteroids (used in the
management of cancer or non-cancer-related illnesses). However, during the
course of the study, use of corticosteroids is allowed if used for treating irAEs or
adrenal insufficiencies;
e) Prior treatment with any inhibitor or agonist of T-cell costimulation;
f) Prior systemic, bone-targeted radioisotope therapy (eg, Strontium-89,
Samarium-153 or similar agents);
6) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of overall survival (OS) will be defined as the time from the date of randomization until the date of death. For those subjects who have not died, OS will be censored at the last date the subject was known to be alive.

E.5.1.1

Timepoint(s) of evaluation of this end point

Assessed at each study visit while on treatment and every 12 weeks
during follow-up.

E.5.2

Secondary end point(s)

(1) Compare Progression Free Survival (PFS) by collecting tumor
assessments every 12 weeks until protocol defined progression or
initiation of subsequent therapy for prostate cancer
(2) Compare time to pain progression by collection of a Patient Pain
Diary prior to each treatment visit and every 12 weeks during follow up
until progression of disease or initiation of subsequent therapy for
prostate cancer
(3) Compare time to subsequent non-hormonal systemic therapy by
collection of subsequent prostate cancer therapies during follow up
(4) Characterize Safety Profile by collection of adverse event information
and review of laboratory values at every study visit

E.5.2.1

Timepoint(s) of evaluation of this end point

(1) Each study visit while on treatment, and every 12 weeks during
follow up until progression of disease or initiation of subsequent therapy
for prostate cancer
(2) Each study visit while on treatment, and every 12 weeks during
follow up until progression of disease or initiation of subsequent therapy
for prostate cancer
(3) Every 12 weeks during follow up until initiation of subequent
nonhormonal systemic therapy for prostate cancer
(4) Continuously throughout study and during follow up until all
toxicities have resolved, returned to baseline or been deemed
irreversible

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity (HAHA); Outcomes Research Assessments; biomarker samples collection

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.8.2.4

Number of treatment arms in the trial

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

Yes

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

Argentina

Australia

Brazil

Canada

Chile

Colombia

Czech Republic

Denmark

France

Germany

Greece

Hungary

Italy

Mexico

Netherlands

Norway

Peru

Poland

Puerto Rico

Romania

Russian Federation

Spain

Sweden

Turkey

United Kingdom

United States

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

For all subjects, contact will be made every 12 weeks to evaluate Overall Survival (OS) and collect data on the initiation of subsequent therapy for prostate cancer.

The final analysis of OS will be performed when 379 events (deaths) have been observed. This is expected to occur ~52 months after the first subject has been randomized. Additional survival follow-up may occur after the final OS analysis to further characterize long-term survival for subjects randomized in this study.

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.1.1.1

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.1.3

Elderly (>=65 years)

Yes

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.4.2

For a multinational trial

F.4.2.1

In the EEA

183

F.4.2.2

In the whole clinical trial

660

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)

Subjects who complete study & continue demonstrating clinical benefit will be eligible to receive study drug (SD). SD will be provided via HA/EC-approved study extension, rollover study or other method at Sponsor discretion. Sponsor reserves the right to terminate access if:
-marketing app. rejected by responsible HA;
-study terminated due to safety concerns;
-subject can obtain SD from government/private health program; or
-therapeutic alternatives available in the local market.

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

2010-10-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-09-28

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