Clinical Trials Register

Summary
EudraCT Number:	2011-000732-29
Sponsor's Protocol Code Number:	CA184-124
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-02-13
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-000732-29

A.3

Full title of the trial

A Randomized, Open-Label, Phase 2 Safety and Efficacy Trial of Ipilimumab versus Pemetrexed in Subjects with Recurrent/Stage IV Non-Squamous, Non-Small Cell Lung Cancer Who Have Not Progressed After Four Cycles of a Platinum-Based First Line chemotherapy

A.3.1

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

Study for the assessment of Safety and Efficacy of treatment with the study medication Ipilimumab in comparison with treatment with Pemetrexed. Affected patients are patients with recurrent / Stage IV NSCLC where the disease did not progress (growth of tumour) after 4 cycles of Chemotherapy treatment with platinum Chemotherapy. Patients are distributed by random to one of the two treatments, but will be aware which treatment they receive.

A.4.1

Sponsor's protocol code number

CA184-124

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	EU Study Start-Up Unit
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 8
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	Concentrate for 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
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	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	Comparator
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	Alimta
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V.
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 concentrate for 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.3.9.1	CAS number	150399-23-8
D.3.9.3	Other descriptive name	PEMETREXED DISODIUM
D.3.9.4	EV Substance Code	SUB03669MIG
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	500
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

NSCLC is the description of a malign development of body tissues from cells in the Bronchia / Lungs where larger cells are visible per microscope.

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

To compare overall survival of subjects who have been randomized to receive ipilimumab at 10mg/kg to that of subjects receiving pemetrexed at 500mg/m2.

E.2.2

Secondary objectives of the trial

To compare progression free survival by mWHO and to evaluate best overall response rate (BORR)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Signed Written Informed Consent:

a) Willing and able to provide informed consent

2) Target Population:

a) Subjects with NSCLC of predominantly non-squamous histology documented by histology or cytology from brushing, washing or needle aspiration of a defined lesion but not from sputum cytology alone
b) Subjects must present with Stage IV or Recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer (IASLC) classification)
c) Subjects must have received 4 cycles of a platinum-based chemotherapy regimen consisting of carboplatin or cisplatin combined with docetaxel, paclitaxel, vinorelbine, gemcitabine, or pemetrexed. Previous treatment with cetuximab or bevacuzimab is allowed provided these drugs are stopped at least 3 weeks prior to randomization.
d) Subjects must have stable disease or better following the 4 cycles of platinum-based chemotherapy
e) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at study entry.
f) Accessible for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating centers

3) Age and Reproductive Status:

a) Men and Women >/= 18 years of age
b) Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of ipilimumab in such a manner that the risk of pregnancy is minimized. See Section 3.3.3 for the definition of WOCBP
c) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product
d) Women must not be breastfeeding

E.4

Principal exclusion criteria

1) Target Disease Exceptions:

a) Brain metastases unless stable with no evidence of progression on scans for at least 30 days, non-symptomatic, and not requiring treatment with steroids
b) Malignant pleural effusion that is recurrent despite appropriate supportive care
c) Known to have an EGFR activating mutation and/or an ALK mutation
d) Have previously been treated with a tyrosine kinase inhibitor (eg., erlotinib, gefintinib, etc)
e) Previously been treated with more than 4 cycles of chemotherapy for recurrent/stage IV lung cancer

2) Medical History and Concurrent Diseases:

a) Documented history of severe autoimmune or immune mediated symptomatic disease that required prolonged (more than 2 months) systemic immunosuppressive (ie, steroids) treatment such as:
i) Ulcerative colitis and Crohn’s di sease
ii) Rheumatoid arthritis, systemic progressive sclerosis (scleroderma)
iii) Systemic Lupus Erythematosus
iv) Autoimmune vasculitis (eg, Wegener’s Granulomatosis)
b) Subjects with history of motor neuropathy considered of autoimmune origin (eg, Guillain Barré Syndrome)
c) Subjects with a history of toxic epidermal necrolysis (TEN)
d) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing questionnaires
e) Serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol therapy
f) Prior malignancy, active within 5 years, except for locally curable cancers that have been apparently cured and need no subsequent therapy, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
g) HIV, Hepatitis B, or Hepatitis C infection based on testing performed during the CA184124 screening period
h) Subjects with >/= Grade 1 peripheral neuropathy

3) Physical and Laboratory Test Findings:

a) Inadequate hematologic function defined by:
i) Absolute neutrophil count (ANC) < 1,500/mm3, or
ii) Platelet count < 100,000/mm3; or
iii) Hemoglobin level < 9 g/dL
b) Inadequate hepatic function as defined by either:
i) Total bilirubin level >/=2.5 times the upper limit of normal (ULN);
ii) AST and ALT levels >/= times the ULN or >/= times the ULN if liver metastases are present
c) Inadequate renal function defined as calculated creatinine clearance < 45 ml/min based on the standard Cockroft and Gault formula

4) Prohibited Treatments and/or Therapies:

a) Chronic use of immuno-suppressive drugs (ie, corticosteroids used in the management of cancer or non-cancer related illnesses). Use of corticosteroids are allowed if used as premedication for chemotherapy administration or on study management of an AE
b) Any non-oncology vaccine therapy, including flu vaccine, used for prevention of infectious disease for up to 4 weeks prior to or after any dose of study drug
c) Any immunotherapy for the treatment of cancer
d) Prior treatment with any inhibitor or agonist of T-cell co-stimulation
e) Unable to interrupt treatment with aspirin or non steroidal inflammatory drugs
f) Unable to take folic acid and vitamin B12

5) Sex and Reproductive Status:

a) Sexually active fertile men not using effective birth control if their partners are WOCBP.

6) Other Exclusion Criteria:

a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

E.5 End points

E.5.1

Primary end point(s)

Overall survival 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 on the last date the subject was known to be alive.

E.5.1.1

Timepoint(s) of evaluation of this end point

Final analysis occurs when we reach 132 deaths. There is an IA at 99 deaths.

E.5.2

Secondary end point(s)

The secondary endpoints are progression-free survival and best overall response rate per mWHO criteria.
• Progression-free survival is defined as the time between the event of disease progression per mWHO criteria or death and the randomization date. If the subject did not progress or die, he/she will be censored at the last tumor assessment date.
• The BORR will be defined as the number of subjects whose best overall response per mWHO criteria was CR or PR, divided by the total number of subjects in the all randomized subjects data set.

E.5.2.1

Timepoint(s) of evaluation of this end point

Final analysis occurs when we reach 132 deaths. There is an IA at 99 deaths.

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

Yes

E.8.1.1

Randomised

Yes

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)

Yes

E.8.2.2

Placebo

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

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

Belgium

France

Germany

Italy

Poland

Russian Federation

Spain

United States

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

Final analysis occurs when we reach 132 deaths.

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

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:

126

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

Yes

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

173

F.4.2.2

In the whole clinical trial

200

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)

Patients who show clinical benefit from the IP will be eligible to continue to receive IP after study has concluded. (study extension). Subjects that do not show this benefit / progressed patients will receive further treatment at the discretion of the PI / sub Investigator.

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

2012-05-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-24

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2012-03-01

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