Clinical Trials Register

Summary
EudraCT Number:	2010-024216-34
Sponsor's Protocol Code Number:	ABCSG 33
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-02-02
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

2010-024216-34

A.3

Full title of the trial

Neoadjuvant Endocrine Treatment +/- Bevacizumab in postmenopausal Patients with Operable Primary, HER2-neu negative Breast Cancer (including Lobular Cancer) (I) not suitable for Chemotherapy or (II) unlikely to respond to Chemotherapy

A.4.1

Sponsor's protocol code number

ABCSG 33

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	ABCSG (Austrian Breast & Colorectal Cancer Study Group)
B.1.3.4	Country	Austria
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	Yes
D.2.1.1.1	Trade name	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Ltd.
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	Avastin
D.3.2	Product code	RO487-6646
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	BEVACIZUMAB
D.3.9.1	CAS number	216974-75-3
D.3.9.2	Current sponsor code	RO487-6646
D.3.9.3	Other descriptive name	rhuMAb, VEGF, anti-VEGF
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	25
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	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	Yes
D.3.11.13.1	Other medicinal product type	recombinant humanized monoclonal antibody
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	Aromasin
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Corporation Austria GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Aromasin
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	Exemestan
D.3.9.1	CAS number	107868-30-4
D.3.9.3	Other descriptive name	EXEMESTANE
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	25
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Postmenopausal women with histologically proven primary breast cancer of stages I-III scheduled for neoadjuvant endocrine treatment, N+/-, M0, HER2 negative; including patients with lobular breast cancer or patients with any breast cancer histology not suitable for chemotherapy or unlikely to respond to chemotherapy

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assessment of efficacy of neoadjuvant bevacizumab in combination with exemestane in postmenopausal patients with hormone receptor positive (ER and/or PR positive) primary breast cancer, as measured by overall clinical response rates and determined by MRT. The overall clinical response (ORR) is defined as the percentage of patients with either a complete clinical response (CR) or a partial clinical response (PR).

E.2.2

Secondary objectives of the trial

Assessment of angiogenic response by DCE-MRT, downstaging rate to breast-conserving surgery, complete pathological response rate

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Female Patients with histologically diagnosed hormone receptor positive (ER and/or PR positive ), HER2/neu negative (IHC < 2+ or FISH negative) operable breast cancer
1. Any condition excluding a patient from chemotherapy but not from endocrine treatment in combination with bevacizumab and therefore allowing patients to enter the study are:
(i) biological age
(ii) ECOG Performance status ≥2
(iii) normal or reduced hematopoietic reserve, but leukocytes >1,500/µl, platelets >1000,000/ µl and Hb ≥8 g/dl
(iv) Normal or reduced renal function but no necessity for dialysis
2. Stage I, II or Stage III (T2-T4a-c, N0-3, M0)
3. Postmenopausal status, defined as:
a) the patient is amenorrhoeic for > 12 months or
b) FSH and estradiol are in postmenopausal range or
c) the patient is 61 years of age or older.
4. No prior chemotherapy, radiotherapy, or endocrine therapy for invasive or non-invasive breast cancer.
5. Normal cardiac function must be confirmed by LVEF (MUGA scan or Echocardiography) within 4 weeks prior to randomization. The result must be above 50% .
6. Signed and dated informed consent
7. Willingness and ability to comply with treatment and all study related procedures

E.4

Principal exclusion criteria

Concomitant conditions
1. Metastatic disease
2. Inflammatory carcinoma (T4d)
3. HER2neu positive breast cancer
4. Prior treatment for breast cancer
5. Active viral, bacterial or fungal infection
6. History of solid organ transplantation
7. CNS involvement by Breast Cancer or any evidence of spinal cord compression. Brain CT/MRI is only mandatory in case of clinical suspicion of CNS involvement by Breast Cancer
8. Prior malignancy (except adequately treated basal cell carcinoma of the skin, in situ cervical cancer, or any other cancer for which the patient has been in remission for at least 5 years)
9. Known hypersensitivity to study drug or its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies)
10. Severe chronic obstructive pulmonary disease with hypoxemia
11. thrombosis unless resolved and under adequate control by anticoagulation (see 24)
12. Uncontrolled hypertension (>150mmHg and/or a diastolic >100 mmHg) or clinically significant (i.e. active) cardiovascular disease (CVA/stroke within <6 months prior to randomization) myocardial infarction within < 6 months prior to randomization, unstable angina pectoris, congestive heart failure (≥ NYHA Grade II), or serious cardiac arrhythmia requiring ongoing medication, NYHA ≥ Grade II
13. Clinically significant, active peripheral vascular disease, serious non healing wound/ulcer, bone fracture, bleeding diathesis (history or evidence of inherited bleeding diathesis) and/or coagulopathy
14. History of active ulcer (within 1 year prior to randomization), abdominal fistula, gastrointestinal perforation, or intraabdominal abscess or concurrent therapy for treatment/prevention of ulcer
15. Evidence of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or patient at high risk from treatment complications
16. Any co-existing medical or psychological condition that would compromise ability to give informed consent
17. Uncontrolled diabetes mellitus
Current treatment
18. Seizures requiring permanent anticonvulsant therapy
19. chronic daily treatment with corticosteroids (dose ≥10 mg/d methylprednisolone or equivalent) with the exception of inhaled steroids
20. chronic daily treatment with acetylsalicylic acid (aspirin or analogs >325 mg/day) or clopidrogel (>75 mg/day)
21. Major surgery, open biopsy or trauma within 28 days before randomization (fine-needle biopsies of breast tissue or lymph node are not considered major surgery), or the need for major surgery during the course of study treatment (adequate time delay of 6 weeks between last cycle of bevacizumab and surgery is considered in the design of the trial)
22. Current or recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational therapeutic study
Laboratory (determined within 7 days prior to day 1 cycle 1)
23. Inadequate liver function, defined as:
- serum (total) bilirubin >1.5 x the upper limit of normal (ULN) for the institution
- AST/SGOT or ALT/SGPT >2,5 x ULN
- ALP >2.5 x ULN at baseline
24. Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) >1.5 or an activated partial thromboplastin time (aPTT) >1.5 x ULN within 7 days prior to first study treatment
25. Inadequate renal function (Proteinuria), defined with Urine dipstick; if dipstick is ≥ 2+ at baseline, the patient must undergo 24-hour urine collection and demonstrate ≤1 g of protein/24 hr)

E.5 End points

E.5.1

Primary end point(s)

Overall Response rate (CR, PR) by MRT

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

overall clinical response, downstaging rate of breast conserving surgery, Quality of life, Survival

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.8.3

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

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

6 month +/- 1 week follow up after surgery. The study ends for the patient with the final follow-up 12 months (=365 days) +/- 1 week after surgery.

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.1.3

Elderly (>=65 years)

Yes

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

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

334

F.4.2

For a multinational trial

F.4.2.1

In the EEA

334

F.4.2.2

In the whole clinical trial

334

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)

Routine follow-up care program with regular check up's at the site.

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

2011-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-15

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2012-03-13

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