Clinical Trials Register

Summary
EudraCT Number:	2011-005547-27
Sponsor's Protocol Code Number:	GO28074
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-08-07
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

Spain - AEMPS

A.2

EudraCT number

2011-005547-27

A.3

Full title of the trial

A PHASE II, MULTICENTER, OPEN-LABEL, RANDOMIZED STUDY EVALUATING THE EFFICACY AND SAFETY OF FOLFIRI + MEHD7945A VERSUS FOLFIRI + CETUXIMAB IN SECOND LINE IN PATIENTS WITH KRAS WILD-TYPE METASTATIC COLORECTAL CANCER

ESTUDIO DE FASE II, ALEATORIZADO, MULTICÉNTRICO Y ABIERTO PARA EVALUAR LA EFICACIA Y LA SEGURIDAD DE FOLFIRI + MEHD7945A FRENTE A FOLFIRI + CETUXIMAB COMO TRATAMIENTO DE SEGUNDA LÍNEA EN PACIENTES CON CÁNCER COLORRECTAL METASTÁSICO CON KRAS ALELO SALVAJE

A.3.1

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

Study of the investigational drug MEHD7945A compared to the anticancer drug cetuximab when combined with standard chemotherapy in patients with colorectal cancer without mutation in the KRAS gene (Kras wild type).

ESTUDIO DEL MEDICAMENTO EN INVESTIGACIÓN MEHD7945A COMPARADO CON CETUXIMAB CUANDO SE COMBINA CON QUIMIOTERAPIA ESTANDAR EN PACIENTES CON CÁNCER COLORRECTAL METASTÁSICO SIN MUTACIÓN EN EL GEN KRAS (CON KRAS ALELO SALVAJE)

A.4.1

Sponsor's protocol code number

GO28074

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	Genentech, Inc.
B.1.3.4	Country	United States
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	Genentech Inc. c/o F. Hoffmann-La Roche Ltd.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genentech Inc. c/o F. Hoffmann-La Roche Ltd.
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	----
B.5.5	Fax number	----
B.5.6	E-mail	global.rochegenentechtrials@roche.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	MEHD7945A
D.3.2	Product code	MEHD7945A (RO5541078)
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	MEHD7945A
D.3.9.2	Current sponsor code	MEHD7945A (RO5541078)
D.3.9.3	Other descriptive name	Anti-HER3/EGFR DAF, DL11f, RO5541078
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	20
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	Erbitux
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.3.4	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	205923564
D.3.9.2	Current sponsor code	RO5469926
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	5
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

Colorectal cancer that does not carry mutation in the KRAS gene

cancer colorrectal sin mutación en gen KRAS

E.1.1.1

Medical condition in easily understood language

Colorectal cancer that does not carry mutation in the KRAS gene

cancer colorrectal sin mutación en gen KRAS

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	10001167
E.1.2	Term	Adenocarcinoma of colon
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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10010029
E.1.2	Term	Colorectal cancer NOS
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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10038019
E.1.2	Term	Rectal adenocarcinoma
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

1-To evaluate the efficacy, as measured by PFS, of FOLFIRI + MEHD7945A (administered every 2 weeks) versus FOLFIRI + cetuximab (administered weekly) in patients with KRAS wild-type mCRC
2- To evaluate the efficacy, as measured by PFS, of FOLFIRI + MEHD7945A (administered every 2 weeks) versus FOLFIRI + cetuximab (administered weekly) in patients with KRAS wild-type mCRC whose tumors express low levels of HER3

? Evaluar la eficacia, medida por la supervivencia libre de progresión (SSP), de FOLFIRI + MEHD7945A (administrados cada 2 semanas) frente a FOLFIRI + cetuximab (administrados cada semana) en pacientes con cáncer colorrectal metastásico (CCRm) con KRAS alelo salvaje
? Evaluar la eficacia, medida por la SSP, de FOLFIRI + MEHD7945A (administrados cada 2 semanas) frente a FOLFIRI + cetuximab (administrados cada semana) en pacientes con CCRm con KRAS alelo salvaje cuyos tumores expresan concentraciones bajas de HER3

E.2.2

Secondary objectives of the trial

?To evaluate the efficacy, as measured by objective response rate, duration of objective response, and overall survival, of FOLFIRI + MEHD7945A (administered every 2 weeks) versus FOLFIRI + cetuximab (administered weekly) in patients with KRAS wild-type mCRC
?To evaluate the efficacy, as measured by objective response rate, duration of objective response, and overall survival, of FOLFIRI + MEHD7945A (administered every 2 weeks) versus FOLFIRI + cetuximab (administered weekly) in patients with KRAS wild-type mCRC whose tumors express low levels of HER3
?To evaluate the efficacy, as measured by PFS, objective response rate, duration of objective response, and overall survival, of FOLFIRI + MEHD7945A (administered every 2 weeks) versus FOLFIRI + cetuximab (administered weekly) in patients with KRAS wild-type mCRC whose tumors express high levels of HRG

Evaluar la eficacia, medida por la tasa de respuesta objetiva, la duración de la respuesta objetiva y la supervivencia global, de FOLFIRI + MEHD7945A (administrados cada 2 semanas) frente a FOLFIRI + cetuximab (administrados cada semana) en pacientes con CCRm con KRAS alelo salvaje
? Evaluar la eficacia, medida por la tasa de respuesta objetiva, la duración de la respuesta objetiva y la supervivencia global, de FOLFIRI + MEHD7945A (administrados cada 2 semanas) frente a FOLFIRI + cetuximab (administrados cada semana) en pacientes con CCRm con KRAS alelo salvaje cuyos tumores expresan concentraciones bajas de HER3
- Evaluar la eficacia, medida por la SSP, la tasa de respuesta objetiva, la duración de la respuesta objetiva y la supervivencia global, de FOLFIRI + MEHD7945A (administrados cada 2 semanas) frente a FOLFIRI + cetuximab (administrados cada semana) en pacientes con CCRm con KRAS alelo salvaje cuyos tumores expresan concentraciones altas de HRG

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

?Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum cancer with wildtype Kras status
?Progressive disease on or after a first-line oxaliplatin-containing chemotherapy regimen for mCRC
?Availability and willingness to provide archival tumor tissue for biomarker testing
?Age ?18 years
?Male and female
?Life expectancy ?12 weeks
?ECOG 0 or 1
?Disease that is measurable per RECIST v1.1
?Adequate hematologic and end-organ function

- Adenocarcinoma de colon o recto con estado de KRAS alelo salvaje confirmado histológica o citológicamente
- Progresión de la enfermedad durante o después de la quimioterapia de primera línea con oxaliplatino para el CCRm
- Consentimiento para proporcionar tejido tumoral de archivo obligatorio para el estudio de biomarcadores
- Edad ? 18 años
- hombres o mujeres
- Esperanza de vida ? 12 semanas
- Estado funcional según la escala ECOG de 0-1
- Enfermedad medible conforme a los criterios RECIST v1.1
- Función hematológica y posibles órganos afectados adecuada

E.4

Principal exclusion criteria

?Prior treatment with irinotecan
?Prior treatment with an investigational or approved HER-targeted agent
?Last anti tumor therapy within 4 weeks prior to Day 1 of the study treatment with exception of oxaliplatin-containing chemotherapy and palliative radiotherapy
?Leptomeningeal disease as the only manifestation of the current malignancy
?Major surgical procedure within 4 weeks prior to Day 1 of the study treatment
?Current severe, uncontrolled systemic disease
?History of cardiac heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment
?History of myocardial infarction within 6 months prior to Day 1 of the study treatment, or history of unstable angina
?Clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; or current alcohol abuse
?Clinically significant gastrointestinal bleeding within 6 months prior to Day 1 of the study treatment
?History of ILD
?History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
?Untreated or progressing CNS metastases
?Women during pregnancy or lactation

Tratamiento previo con irinotecán
? Tratamiento previo con un fármaco dirigido a HER, en investigación o aprobado
? Último tratamiento antineoplásico en las 4 semanas anteriores al día 1 del ciclo 1, incluyendo quimioterapia, tratamientos biológicos, en investigación u hormonales, o radioterapia
Intervención de cirugía mayor en las 4 semanas anteriores al día 1 del ciclo 1
? Enfermedad leptomeníngea como única manifestación de la neoplasia maligna actual
- Enfermedad generalizada actual grave no controlada
- Antecedentes de insuficiencia cardiaca de cualquier grado según la New York Heart Association o arritmia cardiaca grave que precise tratamiento
- Antecedentes de infarto de miocardio en los 6 meses anteriores al día 1 del ciclo 1 o antecedentes de angina de pecho inestable.
? Hepatopatía conocida clínicamente significativa, como hepatitis activa viral, alcohólica o de otro tipo, cirrosis o alcoholismo actual
- Hemorragia digestiva clínicamente significativa en los 6 meses anteriores al día 1 del ciclo 1
- Antecedentes de reacción alérgica o hipersensibilidad intensa (de grados 3 o 4) a anticuerpos terapéuticos que haya requerido la interrupción del tratamiento
-Metástasis del SNC no tratadas/activas
-Embarazo o lactancia

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this study is PFS which will be determined for all patients and for subset of biomarker-positive patients with Kras wild type mCRC. PFS is defined as the time from randomization to documented disease progression assessed by the investigator or death on study, whichever occurs first.

El criterio principal de valoración en este estudio es la SSP en todos los pacientes con CCRm en todos los pacientes con CCRm con KRAS alelo salvaje y en pacientes con CCRm con KRAS alelo salvaje cuyos tumores expresen concentraciones bajas de HER3). La SSP se define desde la randomización a la ELP valorada por el investigador o la muerte en el estudi, lo que ocurra primero.

E.5.1.1

Timepoint(s) of evaluation of this end point

See section E.5.1

ver sección E.5.1

E.5.2

Secondary end point(s)

?Objective response, duration of objective response, and overall survival for all patients and for subset of biomarker-positive patients with Kras wild type mCRC.
?Incidence, nature, and severity of adverse events, graded according to the NCI CTCAE v4.0
?Clinically significant changes in vital signs, physical findings, and clinical laboratory results during and following administration of study treatment
?MEHD7945A minimum (Cmin) and maximum (Cmax) serum concentration prior to and after infusion at select time points for patients on Arm A
?Plasma concentrations of 5-FU, irinotecan, and SN-38 prior to and after infusion at select time points for patients on Arm A
?Serum anti-therapy antibodies (ATAs) to MEHD7945A prior to infusion at select time points for patients on Arm A

E.5.2.1

Timepoint(s) of evaluation of this end point

See section E.5.2

Ver sección E.5.2

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

Yes

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

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)

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

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

Australia

Belgium

Canada

France

Germany

Italy

Romania

Spain

United Kingdom

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

This study will be considered completed at the time of the last scheduled clinic visit for the last patient in study, or the date at which the last data point required for efficacy analysis or safety follow up is received and confirmed, whichever is later.

LVLS, o la fecha en la que se recibe y se confirma el último dato requerido para análisis del seguimiento de eficacia o seguridad, lo que ocurra más tarde.

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.1.2.1

Number of subjects for this age range:

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

F.4.2.2

In the whole clinical trial

120

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 have shown a demonstrable benefit from MEHD7945A treatment during this study may be given the opportunity to continue MEHD7945A treatment as part of an extension study.

Pacientes que demuestren beneficio del tratamiento con MEHD7945A durante el estudio pueden tener la oportundiad de continuar con tratamiento MEHD7945A como parte de un estudio de extensión.

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

2012-11-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-09

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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