Clinical Trials Register

Summary
EudraCT Number:	2014-001458-40
Sponsor's Protocol Code Number:	BO29159
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-01-07
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-001458-40

A.3

Full title of the trial

A MULTICENTER, OPEN-LABEL, SINGLE-ARM SAFETY STUDY OF HERCEPTIN® SC IN COMBINATION WITH PERJETA® AND DOCETAXEL IN TREATMENT OF PATIENTS WITH HER2−POSITIVE ADVANCED BREAST CANCER (METASTATIC OR LOCALLY RECURRENT)

A.3.1

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

Phase IIIb Study to Evaluate the Safety and Tolerability of Herceptin SC with Perjeta and Docetaxel in Patients with HER2-positive Advanced Breast Cancer

A.3.2

Name or abbreviated title of the trial where available

MetaPHer

A.4.1

Sponsor's protocol code number

BO29159

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	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	Grenzacherstrassen 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
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	Yes
D.2.1.1.1	Trade name	Herceptin 600 mg/5 mL solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, U.K.
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.3.2	Product code	Ro 045-2317/F07
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	RO0452317
D.3.9.3	Other descriptive name	rhuMAb HER2, Anti-HER
D.3.9.4	EV Substance Code	SUB12612MIG
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	120
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	Yes
D.2.1.1.1	Trade name	Perjeta
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited, UK
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	Pertuzumab (rhuMAb 2C4)
D.3.2	Product code	Ro 436-8451/F01
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	Pertuzumab
D.3.9.1	CAS number	380610-27-5
D.3.9.2	Current sponsor code	RO4368451
D.3.9.3	Other descriptive name	PERTUZUMAB
D.3.9.4	EV Substance Code	SUB16455MIG
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	30
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

HER2−POSITIVE METASTATIC OR LOCALLY RECURRENT ADVANCED BREAST CANCER

E.1.1.1

Medical condition in easily understood language

Breast 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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10065430
E.1.2	Term	HER-2 positive breast 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

The primary objective for this study is to evaluate the safety and tolerability of Herceptin SC in combination with Perjeta IV plus docetaxel in patients with HER2−positive advanced (metastatic or locally recurrent) breast cancer.
• Overall safety profile as determined by adverse events of any grade of severity, and adverse events Grade ≥ 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 and cardiac function will be assessed including the following: cardiac events Grade ≥ 3, congestive heart failure (CHF), and cardiac death

E.2.2

Secondary objectives of the trial

The secondary objectives for this study are to evaluate Herceptin SC in combination with Perjeta IV plus docetaxel with respect to:
• Efficacy parameters
PFS
OS
Objective Response Rate (ORR)
• Incidence of anti-Herceptin and anti-rHuPH20 antibody formation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection. Patients with measurable and/or non-measurable disease evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 are eligible.
- HER2-positive disease (defined as either immunohistochemistry [IHC] 3 + or in situ hybridization [ISH] positive) as assessed by local laboratory on primary tumor or metastatic site if primary tumor not available
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Left ventricular ejection fraction (LVEF) of at least 50%
- Negative serum pregnancy test result at baseline and use of effective contraception as defined by the protocol

E.4

Principal exclusion criteria

Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease. Note: Prior to study entry, up to two lines of hormonal therapy for metastatic or locally recurrent disease are permitted, one of which may be in combination with everolimus.
- Disease-free interval of at least 6 months from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of breast cancer
- Previous approved or investigative anti-HER2 agents as neoadjuvant or adjuvant therapy for any breast cancer treatment, except Herceptin
- History of persistent Grade 2 or higher hematological toxicity resulting from previous adjuvant or neoadjuvant therapy
- Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI), unless they have been treated and have been stable for at least 3 months and do not require ongoing corticosteroid treatment
- Current peripheral neuropathy of Grade 3 or greater
- History of other malignancy within the last 5 years prior to first dose of study drug administration, except for carcinoma in situ of the cervix or basal cell carcinoma
- Inadequate organ function
- Uncontrolled hypertension with or without medication
- Clinically significant cardiovascular disease
- History of LVEF decline to below 50% during or after prior Herceptin neo-adjuvant or adjuvant therapy
- Current known infection with HIV, hepatitis B virus, or hepatitis C virus
- Severe uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for treatment-related complications, including severe pulmonary conditions/illness
- Pregnant or lactating women
- Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy
- History of receiving any investigational treatment within 28 days prior to first dose of study drug administration (dosing) or concurrent participation in any interventional clinical trial

E.5 End points

E.5.1

Primary end point(s)

- Incidence and severity of adverse events Grade >/= 3, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0
- Incidence of cardiac events (composite outcome measure): congestive heart failure (CHF) and cardiac death
- Incidence of adverse events (AEs)

E.5.1.1

Timepoint(s) of evaluation of this end point

- Timeframe: Up to 24 months after the last patient has been enrolled, approximately 3.5 years
- Timeframe: Up to 24 months after the last patient has been enrolled, approximately 3.5 years
- Timeframe: Up to 24 months after the last patient has been enrolled, approximately 3.5 years

E.5.2

Secondary end point(s)

- Progression-free survival, tumor assessments according to RECIST v1.1
- Overall survival
- Objective response rate, defined as a complete response (CR) or a partial response (PR)
- Outcome Measure: Incidence of anti-Herceptin, anti-rHuPH20 antibodies

E.5.2.1

Timepoint(s) of evaluation of this end point

- Timeframe: Up to 3.5 years
- Timeframe: Up to 3.5 years
- Timeframe: Up to 3.5 years
- Timeframe: Up to 3.5 years

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

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

- tolerability of Herceptin subcutaneous (SC) in combination with Perjeta intravenous (IV) plus docetaxel
- Incidence of anti-Herceptin and anti-rHuPH20 antibody formation

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

E.8.1.1

Randomised

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

Yes

E.8.1.7.1

Other trial design description

safety and tolerability of Herceptin SC in comb. with Perjeta/docetaxel

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

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

115

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

study will end at the time of the cutoff for final analysis, 24 months after last patient has been enrolled, or all patients in study have withdrawn consent, died, or if the study is prematurely terminated by the Sponsor, whichever occurs first.
patients still receiving study treatment at time of cutoff will have their post-treatment safety follow-up visit 28−35 days after the last dose of study treatment, and then will be considered as finished with their participation in the 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.1.2.1

Number of subjects for this age range:

336

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

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

400

F.4.2.2

In the whole clinical trial

400

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 will continue to be followed in accordance with the local standard of care.
These patients may be provided with commercial drug for continuation of treatment. This will depend on the local availability of commercial Herceptin and Perjeta.
The Sponsor will offer post-trial access to the study drug Herceptin and Perjeta free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, see section 4.3.4 of protocol.

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

2015-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-15

P. End of Trial
P.	End of Trial Status	Completed

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