Clinical Trials Register

Summary
EudraCT Number:	2013-001023-39
Sponsor's Protocol Code Number:	ML28786
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2013-07-01
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

Austria - BASG

A.2

EudraCT number

2013-001023-39

A.3

Full title of the trial

LISAH: AN OPEN-LABEL, RANDOMISED PHASE II STUDY ASSESSING QUALITY OF LIFE ASSOCIATED WITH SUBCUTANEOUS TRASTUZUMAB INJECTED INTO THE THIGH OR UPPER ARM IN PATIENTS WITH HER2-POSITIVE EARLY BREAST CANCER

A.3.1

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

A study to evaluate the impact on the quality of life and the safety and tolerability of trastuzumab given in a new, subcutaneous way (injection into fatty tissue just under your skin)

A.3.2

Name or abbreviated title of the trial where available

LISAH

A.4.1

Sponsor's protocol code number

ML28786

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	Roche Austria GmbH
B.1.3.4	Country	Austria
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 AG
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Roche Austria GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Roche Austria GmbH
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Engelhorngasse 3
B.5.3.2	Town/ city	Wien
B.5.3.3	Post code	1210
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43127739 0
B.5.5	Fax number	+43127739 254
B.5.6	E-mail	pharma.austria@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	Trastuzumab sc
D.3.2	Product code	RO452317
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	Ro 45-2317/F07
D.3.9.4	EV Substance Code	SUB12612MIG
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	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)	Information not present in EudraCT
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	Information not present in EudraCT
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	Information not present in EudraCT
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	Humanized monoclonal antibody
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	Herceptin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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	Herceptin
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	Intracavernous 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	Ro 45-2317
D.3.9.4	EV Substance Code	SUB12612MIG
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	150
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)	Information not present in EudraCT
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	Information not present in EudraCT
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	Humanised Monoclonal Antibody

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 early breast cancer

E.1.1.1

Medical condition in easily understood language

early stage of a special type of 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	16.0
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

To assess the Quality of Life in HER2-positive eBC patients treated with trastuzumab solution injected subcutaneously into the thigh vs upper arm

E.2.2

Secondary objectives of the trial

To characterize the pharmacokinetics of trastuzumab (Ctrough, Cmax, Tmax, AUC) following subcutaneous injection at the thigh and upper arm.
To determine HCP’s satisfaction of trastuzumab solution injected subcutaneously into the thigh vs upper arm
To determine patient’s satisfaction and preference of injection method and of injection site of trastuzumab solution injected subcutaneously (Questionnaires at trastuzumab Cycle 10 and 14 and decision of injection site of trastuzumab injected subcutaneously after Cycle 14)
To determine efficacy (overall survival and disease free survival)
To determine safety and tolerability of trastuzumab solution injected subcutaneously
Exposure to study medication
Duration of treatment, follow-up

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female and male patients aged ≥ 18 years
2. Signed informed consent prior to any study specific procedure
3. Able and willing to comply with protocol
4. Eastern Cooperative Oncology Group (ECOG) performance status 0–1
5. Hormonal therapy will be allowed as per institutional guidelines
6. Patients must be trastuzumab naïve
7. Left ventricular ejection fraction (LVEF) of ≥ 55% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC, or, for those who were receiving trastuzumab when beginning the study, documented results within an acceptable limit from a cardiac assessment within 3 months prior to enrolment
8. HER2-positive disease immunohistochemistry (IHC)3+ or in situ hybridization (ISH) positive as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay
9. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
10. No evidence of residual, locally recurrent or metastatic disease after completion of surgery and chemotherapy, or during concurrent chemotherapy (neo-adjuvant or adjuvant)
11. Use of concurrent curative radiotherapy will be permitted

E.4

Principal exclusion criteria

1. History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and patients with other curatively treated malignancies who have been disease-free for at least 5 years, are eligible
2. Patients with severe dyspnea at rest or requiring supplementary oxygen therapy
3. Patients with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
4. Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), diagnosed poorly controlled hypertension
5. Pregnant or lactating women. Positive serum pregnancy test in women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause, within 7 days prior to the first dose of study drug
6. Women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause (unless surgically sterile), and male patients with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment. In this study, menopause is defined as a minimum of 12 consecutive months of amenorrhea during which time no other biological or physiological cause had been identified as a potential cause of this state. Examples of adequate contraceptive measures are intrauterine device, barrier method (condoms, diaphragm) also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not acceptable
7. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
8. Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin® including hyaluronidase, or a history of severe allergic or immunological reactions, e.g. difficult to control asthma
9. Patients assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol
10. Inadequate bone marrow function (as indicated by any of the following):
a) Absolute neutrophil count (ANC) < 1,500 / mm3 (< 1.5 × 109/L)
b) Platelets < 100,000 / mm3 (< 100 × 109/L)
c) Hemoglobin < 10 g/dL
11. Impaired hepatic function (as indicated by any of the following):
a) Serum total bilirubin > 1.5 × upper limit of normal (ULN)
b) Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) > 2.5 × ULN
c) Alkaline phosphatase (ALP) > 2.5 × ULN
12. Inadequate renal function, as indicated by serum creatinine > 1.5 × ULN

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint 1:
Ø QoL-VAS (QoL-VAS: Assessment of Quality of Life by Visual Analogue Scale: Range: 0-10; 0 = no influence on QoL by injection, 10 = worst imaginable influence on QoL by injection; Ø QoL-VAS: mean value of the QoL-VAS assessed 21 days after each injection at Cycle 7-10 or at Cycle 11-14)

Primary Endpoint 2:
max QoL-VAS (QoL-VAS: Assessment of Quality of Life by Visual Analogue Scale: Range: 0-10; 0 = no influence on QoL by injection, 10 = worst imaginable influence on QoL by injection; max QoL-VAS: highest value of the QoL-VAS assessed 21 days after each injection at Cycle 7-10 or at Cycle 11-14)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary analysis will be undertaken once all patients have completed the study (treatment phase and 28-days safety follow-up visit).

E.5.2

Secondary end point(s)

• Trastuzumab Pharmacokinetics: Ctrough, Cmax, Tmax and AUC
• Efficacy-parameter: OS and DFS
• Satisfaction and preference parameter:
items of the Questionnaires (Cycles 10 and 14)
patient’s decision of injection site after Cycle 14
HCP satisfaction
• QoL parameter:
QoL-VAS at Cycles 7-14
• Safety parameter: ADR; SAE, AE

E.5.2.1

Timepoint(s) of evaluation of this end point

The primary analysis will be undertaken once all patients have completed the study (treatment phase and 28-days safety follow-up visit).

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

E.8.1.6

Cross over

Yes

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

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

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

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

last follow up visist of the last patient

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

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

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

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.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)

none

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-08-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-15

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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