Clinical Trials Register

Summary
EudraCT Number:	2007-006031-30
Sponsor's Protocol Code Number:	GIM8 OVER
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2009-01-21
Trial 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

2007-006031-30

A.3

Full title of the trial

A Randomized Trial with factorial Design comparing Fulvestrant ± Lapatinib ± Aromatase Inhibitor in metastatic breast cancer progressing after Aromatase Inhibitor therapy

A.3.2

Name or abbreviated title of the trial where available

OVER

A.4.1

Sponsor's protocol code number

GIM8 OVER

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	CONSORZIO ONCOTECH
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	lapatinib
D.3.2	Product code	GW572016
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	lapatinib
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	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

breast cancer

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer

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 compare the Progression Free Survival (PFS) of ARM 1 + ARM 2 vs ARM 3 + ARM 4 and ARM 2 + ARM 4 vs ARM 1 + ARM 3.

Progression free survival (PFS): it is defined as the time between the first study dose administration and the date of progression of the disease or death from any cause, whichever occurs first.

E.2.2

Secondary objectives of the trial

To compare Time To Progression (TTP) of ARM 1 + ARM 2 vs ARM 3 + ARM 4 and ARM 2 + ARM 4 vs ARM 1 + ARM 3
Time to Progression (TTP): it is defined as the time between the first study dose administration and the date of progression of the disease or cancer-related death, whichever occurs first.
To compare Overall Survival (OS) of ARM 1 + ARM 2 vs ARM 3 + ARM 4 and ARM 2 + ARM 4 vs ARM 1 + ARM 3
Overall survival. (OS): it is defined as the time between the first study dose administration and the date death from any cause.
To compare Response Rate of ARM 1 + ARM 2 vs ARM 3 + ARM 4 and ARM 2 + ARM 4 vs ARM 1 + ARM 3
Response Rate: It will be classified according to the RECIST criteria.
To compare Clinical Benefit rate of ARM 1 + ARM 2 vs ARM 3 + ARM 4 and ARM 2 + ARM 4 vs ARM 1 + ARM 3
Clinical Benefit Rate: it is defined as the sum of rates of PR, CR and SD lasting &#8805; 6 months.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of written informed consent
2. Histological/cytological confirmation of breast cancer
3. Documented positive hormone receptor status (ER+ve and/or PgR+ve) of primary or metastaic tumor issue, according to the local laboratory parameters
4. Postmenopausal women, defined as a woman fulfilling any 1 of the following criteria:
&#61607; Aged &#61619; 60
&#61607; Aged 45-59 and satisfying one or more of the following criteria
amenorrhea for &#61619;12 months and intact uterus;
amenorrhea for &#61500;12 months and FSH* within the postmenopausal range, including:
&#61607; pts with hysterectomy
&#61607; pts who have received HRT
&#61607; pts with chemotherapy-induced amenorrhea
&#61607; bilateral oophorectomy at any age >18 years.
*In patients who have previously been treated with an LH-RH analogue, the last depot must have been administered more than 4 months prior to randomization and menses must not have restarted
5. Confirmed progression of disease after an adjuvant therapy or a therapy for metastatic disease with an aromatase inhibitors
6. Patients demonstrating prior response to AI therapy (AI response >2y on adjuvant AI, or CR, PR, SD> 24weeks if receiving AI for advanced disease)
7. Patients fulfilling one of the following criteria:
Patients with measurable disease as per RECIST criteria. This is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as &#8805; 20 mm with conventional techniques or as &#8805; 10 mm with spiral CT scan
Patients with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST criteria. Bone lesions must be evaluable by plain X-ray, CT or MRI. Patients with lesions identified only on radionucleotide bone scan are not eligible.
8. May have received prior radiotherapy as treatment for primary or metastatic tumour; however, is not required for study entry;
9. Life expectancy of at least 8 months in the best judgement of the investigator
10. WHO performance status 0, 1 or 2
11. Patients with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin;
12. Are able to swallow and retain oral medication;

E.4

Principal exclusion criteria

1. Previous therapy with Fulvestrant and/or Lapatinib;
2. Patients with HER 2 overexpressing, either IHC 3+ or FISH +;
3. Concurrent non study anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication; the treatment with bisphosfonates is admitted;
4. Have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
5. Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded;
6. Have a concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient safety;
7. Have an active or uncontrolled infection;
8. Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
9. Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF;
10. Receive concurrent treatment with an investigational agent or participate in another clinical trial;
11.Receive concurrent treatment with prohibited medications (refer to Section 8.2 for details on prohibited medications);
12.Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication;
13.Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to fulvestrant, aromatase inhibitors or lapatinib or excipients.

E.5 End points

E.5.1

Primary end point(s)

disease progression

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

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

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Information not present in EudraCT

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-01-21.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	396

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

2007-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-11-07

P. End of Trial
P.	End of Trial Status	Ongoing

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