ICH GCP - EU Clinical trials Registry - 2004-000137-11 (ES)

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Summary
EudraCT Number:	2004-000137-11
Sponsor's Protocol Code Number:	EMR62202-013
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-06-08
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

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2004-000137-11

A.3

Full title of the trial

Open, randomized, controlled, multicenter phase III study comparing 5-FU/FA plus irinotecan plus cetuximab versus 5-FU/FA plus irinotecan as first-line treatment for epidermal growth factor receptor-expressing metastatic colorectal cancer.

A.3.1

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

Open, randomized, controlled, multicenter study comparing 5-FU/FA plus irinotecan plus cetuximab versus 5-FU/FA plus irinotecan in metastaic colorectal cancer as first-line treatment.

A.3.2

Name or abbreviated title of the trial where available

CRYSTAL

A.4.1

Sponsor's protocol code number

EMR62202-013

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	Merck KGaA
B.1.3.4	Country	Germany
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	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck KGaA
B.5.2	Functional name of contact point	Communication Center
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Landstraße 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496151725200
B.5.5	Fax number	+496151722000
B.5.6	E-mail	service@merck.de

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	Erbitux 2 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck KGaA
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.3.1	Product name	Erbitux
D.3.2	Product code	EMD271786
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	Cetuximab
D.3.9.1	CAS number	205923-56-4
D.3.9.2	Current sponsor code	EMD271786
D.3.9.3	Other descriptive name	C225
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	2
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.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

First-line treatment for epidermal growth factor receptor-expressing metastatic colorectal cancer

E.1.1.1

Medical condition in easily understood language

Metastatic colorectal cancer as first-line treatment

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10052362
E.1.2	Term	Metastatic colorectal 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 whether the progression-free survival time under 5-FU/FA plus irinotecan plus cetuximab is longer than that under 5-FU/FA plus irinotecan as first-line treatment for epidermal growth factor receptor-expressing metastatic colorectal cancer.

E.2.2

Secondary objectives of the trial

To compare between the 2 treatment groups for:
Overall survival time
Response rate (modified WHO criteria)
Disease control rate
To determine:
Duration of response
Quality of life (EORTC QLQ-C30 Questionnaire)
Safety.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inpatient or outpatient ≥18 years of age
Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
1st occurrence of metastatic disease (not curatively resectable)
Immunohistochemical evidence of epidermal growth factor receptor Expression in tumor tissue
Life expectancy of at least 12 weeks
Presence of at least 1 bi-dimensionally measurable index lesion (not lie in an irradiated area)
ECOG performance status of ≤2 at study entry
Effective contraception for both male and female patients if the risk of conception exists
White blood cell count ≥3 x 10E9/L with neutrophils ≥1.5 x 10E9/L, platelet count ≥100 x 10E9/L, hemoglobin ≥5.6 mmol/L (9 g/dL)
Total bilirubin ≤1.5 x upper reference range·
AST ≤2.5 x upper reference range, or ≤5 x upper reference range in case of liver metastasis·
Serum creatinine ≤1.5 x upper reference range·
Recovery from relevant toxicity to previous treatment before study entry.

E.4

Principal exclusion criteria

Previous exposure to epidermal growth factor targeting therapy
Previous irinotecan-based chemotherapy
Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated >6 months before the start of treatment in this study
Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
Concurrent chronic systemic immune therapy or hormone therapy not indicated in this study protocol except for physiologic replacement Known hypersensitivity reaction to any of the components of study treatments·
Pregnancy (absence to be confirmed by ß-hCG test) or lactation period
Brain metastasis and leptomeningeal disease (known or suspected)
Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia·
Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
Previous malignancy other than colorectal cancer in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival

E.5.1.1

Timepoint(s) of evaluation of this end point

The final analyses on PFS time will be conducted after the following 2
conditions have been met: 4 months have elapsed since the last patient was randomized
and 633 patients have radiological evidence of PD.

E.5.2

Secondary end point(s)

Overall survival time
• Best overall response
• Duration of response
• Disease control rate
• Time to response
• Quality of life

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints response rate, disease control rate, and duration of response will be conducted after the following 2 conditions have been met: 4 months have elapsed since the last patient was randomized and 633 patients have radiological evidence of PD. Final analyses of survival and safety will be conducted at the end of the 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

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of life

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

5-FU/FA and irinotecan

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

164

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

Bulgaria

Chile

Hong Kong

Israel

Korea, Democratic People's Republic of

Mexico

Russian Federation

Singapore

South Africa

Taiwan

Ukraine

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 trial will occur, when the following conditions are met:
·The last patient received last dose of study treatment and
·At least 705 events (deaths) have been observed and
·A minimum follow-up of 40 days (five times the upper range of half-lives of cetuximab)

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

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:

751

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

446

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

850

F.4.2.2

In the whole clinical trial

1300

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)

According to investigator's choice

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

2004-10-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2004-09-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-03-24

Clinical Trials Nct-pagina

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