Clinical Trials Register

Summary
EudraCT Number:	2011-005547-27
Sponsor's Protocol Code Number:	GO28074
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-10-26
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

Italy - Italian Medicines Agency

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

UNO STUDIO MULTICENTRICO DI FASE II, RANDOMIZZATO, IN APERTO PER VALUTARE L'EFFICACIA E LA SICUREZZA DELLA TERAPIA FOLFIRI + MEHD7945A RISPETTO A FOLFIRI + CETUXIMAB DI SECONDA LINEA IN PAZIENTI CON CARCINOMA COLORETTALE METASTATICO KRAS NON MUTATO

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).

Studio con il farmaco sperimentale MEHD7945A confrontato con il farmaco antitumorale Cetuximab, associato alla chemioterapia standard, in pazienti con cancro colorettale senza mutazione del gene KRAS (Kras wild type)

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	Roche S.p.A.
B.5.2	Functional name of contact point	Country Head Clin. Ops. Italy
B.5.3	Address:
B.5.3.1	Street Address	Viale G. B. Stucchi 110
B.5.3.2	Town/ city	Monza
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	039 2475070
B.5.5	Fax number	039 2475085
B.5.6	E-mail	sergio.scaccabarozzi@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	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
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo Monoclonale umano IgG1
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	Germany
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	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	RO5469926
D.3.9.4	EV Substance Code	SUB01178MIG
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

cancro colorettale senza mutazione del gene KRAS

E.1.1.1

Medical condition in easily understood language

Colorectal cancer that does not carry mutation in the KRAS gene

cancro colorettale senza mutazione del gene 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.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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

• Valutare l’efficacia, misurata tramite la sopravvivenza libera da progressione, della terapia FOLFIRI + MEHD7945A (somministrata ogni 2 settimane) rispetto a FOLFIRI + cetuximab (somministrata ogni settimana) in pazienti con carcinoma colorettale metastatico (mCRC) KRAS non mutato • Valutare l’efficacia, misurata tramite la sopravvivenza libera da progressione, della terapia FOLFIRI + MEHD7945A (somministrata ogni 2 settimane) rispetto a FOLFIRI + cetuximab (somministrata ogni settimana) in pazienti mCRC KRAS non mutato i cui tumori esprimono livelli bassi di 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

• Valutare l’efficacia, misurata tramite il tasso di risposta obiettiva, la durata della risposta obiettiva e la sopravvivenza complessiva, di FOLFIRI+MEHD7945A (somministrato ogni 2sett) rispetto a FOLFIRI+cetuximab (somministrato ogni sett) in pazienti con mCRC KRAS non mutato •Valutare l’efficacia, misurata tramite il tasso di risposta obiettiva, la durata della risposta obiettiva e la sopravvivenza complessiva, di FOLFIRI+MEHD7945A (somministrato ogni 2sett) rispetto a FOLFIRI+cetuximab (somministrato ogni sett) in pazienti con mCRC KRAS non mutato i cui tumori esprimono livelli bassi di HER3 •Valutare l’efficacia, misurata tramite la PFS, la durata della risposta obiettiva e la sopravvivenza complessiva, di FOLFIRI+MEHD7945A (somministrato ogni 2sett) rispetto a FOLFIRI+cetuximab (somministrato ogni sett) in pazienti con mCRC KRAS non mutato e tumori con alti livelli di 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

• Avere avuto una diagnosi confermata da istologia o citologia di adenocarcinoma del colon e/o del retto, con gene KRAS non mutato. • Progressione della malattia in occasione o dopo chemioterapia di prima linea con oxaliplatino • Consenso a fornire obbligatoriamente tessuto tumorale per archiviazione, per la determinazione dei biomarker • maschi e fammine di età ≥18 anni • Aspettativa di vita ≥12 settimane • Stato prestazionale ECOG di 0 o 1 • Patologia misurabile secondo RECIST v1.1 • Adeguata funzionalità ematologica e d'organo

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

• Trattamenti precedenti con irinotecano • Trattamenti precedenti con un agente sperimentale o approvato a target HER • Ultima terapia antitumorale nelle 4 settimane precedenti il ciclo 1, giorno 1, ad eccezione di chemioterapia con oxaliplatino e radioterapia palliativa. • Patologia leptomeningea come unica manifestazione della neoplasia in corso

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for this study is PFS. PFS is defined as the time from randomization to documented disease progression assessed by the investigator or death on study, whichever occurs first.

La misura di outcome principale relativa all'efficacia di questo studio è la PFS. La sopravvivenza libera da progressione è definita come il tempo intercorso tra la randomizzazione e la progressione della malattia rilevata dallo sperimentatore, o la morte in base all'evento che si verifica prima

E.5.1.1

Timepoint(s) of evaluation of this end point

see section Primary end point(s)

Per l'indicazione del tempo rilevazione di questo end-point si fassia riferimento alla sezione End point primario/i

E.5.2

Secondary end point(s)

•Objective response, duration of objective response, and overall survival. •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

Le misure di outcome relative all’efficacia secondarie sono: -la risposta obiettiva, la durata della risposta obiettiva e la durata della sopravvivenza complessiva. -Incidenza, natura e severità degli eventi avversi, con gradazione in base ai CTCAE NCI v.4.0 -Modifiche clinicamente significative dei segni vitali, dei riscontri obiettivi e dei risultati clinici di laboratorio durante e dopo la somministrazione del trattamento dello studio. -Concentrazione serica minima (Cmin) e massima (Cmax) di MEHD7945A misurata a definiti intervalli di tempo prima e dopo l'infusione per pazienti del braccio A -Concentrazioni plasmatiche di 5-FU, irinotecano e SN-38 misurata a definiti intervalli di tempo prima e dopo l'infusione per pazienti del braccio A -La misura di outcome relativa all’immunogenicità è costituita dagli anticorpi anti-terapeutici serici al MEHD7945A.

E.5.2.1

Timepoint(s) of evaluation of this end point

see section Primary end point(s)

Per l'indicazione del tempo rilevazione di questo end-point si fassia riferimento alla sezione End point primario/i

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

Canada

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.

lo studio verrà considerato concluso al momento dell'ultima visita dell'ultimo paziente, oppure all'ottenimento dell'ultimo data point per l'analisi di efficacia o al raggiungimetnto del follow-up di sicurezza, quale si verifichi per ultimo

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

Number of subjects for this age range:

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.

Ai pazienti che avranno dimostrato un baneficio a seguito del trattamento con MEHD7945A verrà data la possibilità di continuare il trattamento come parte di uno studio di estensione

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

2012-10-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-24

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials