Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Luc Dirix


Contact details

Oncology Centre
St. Augustinus Hospital
Oosterveldlaan 24

Additional identifiers

EudraCT number number

Protocol/serial number

Version V, October 26, 2006

Study information

Scientific title

A open-label stratified phase II study in patients with hormone receptor positive breast cancer with bortezomib (Velcade®) in the reversal of endocrine resistance



Study hypothesis

In this study proposal, the question is asked whether inhibition of the proteasome by bortezomib (Velcade®) might lead to regained disease control in patients with either primary endocrine resistance or acquired endocrine resistance, either on a selective estrogen receptor modulators (SERM) or an aromatase inhibitor (AI).

Ethics approval

The study was approved by the Institutional Review Board/Ethical Committee of the St. Augustinus Hospital on 11th January 2007 (reference number 06/12/08)

Study design

Open-label stratified phase II study

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web fomat, please use the contact details below to request a patient information sheet


Breast cancer -metastatic, hormone receptor positive


Velcade® will be administered on days 1, 8, 15, 22 of a 5 week regimen at a dose of 1.6 mg/sq m on each treatment day.

Intervention type



Phase II

Drug names

Bortezomib (Velcade®)

Primary outcome measure

To evaluate whether the addition of bortezomib (Velcade®) to a SERM or AI will show radiologically documented activity in patients with progressive disease on the identical endocrine agent. This endpoint will be evaluated by radiological evaluation according to RECIST criteria every treatment cycle.

Secondary outcome measures

To elucidate the activity of the NF-kappa B transcription initiated pathway in tumors and blood samples (if available) of patients experiencing endocrine resistance and to demonstrate whether these activities are changed by the treatment with bortezomib. These will include plasma/serum levels of VEGF, IL6, IL8 and 20S proteasome activity in whole blood/available tumour samples.

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Female patients aged more than18 years with metastatic breast cancer
2. Postmenopausal status defined as either
2.1. Age more than 55 years
2.2. Bilateral ovariectomy
2.3. Age less than 55 years with menopausal follicle stimulating hormone (FSH) levels
2.4. Patients on luteinizing hormone-releasing hormone (LH-RH) agonists in combination with either SERM or AI must continue the LHRH agonist
3. ER and/or PgR + disease (at least 10% of nuclei in the initial are either ER or PgR positive) as defined in the participating institution
4. Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST)
5. All patients should have been treated either in the adjuvant or metastatic setting with tamoxifen and an AI
6. Radiologically documented disease progression of disease as defined by RECIST criteria after second line (if prior adjuvant endocrine treatment and relapse within 12 months of stopping this treatment, this can be considered a resistance to this agent) endocrine treatment for metastatic disease being either tamoxifen or any aromatase inhibitor (AI), with patients still considered to be suitable candidates for a third line endocrine treatment
7. Superficial measurable lesions will be included as measurable, provided it is photographed
8. Patients need to be on this endocrine treatment for at least three months in order to clearly document endocrine resistance and exclude as much as possible late responses
9. Disease progression has to documented on consecutive radiological examinations or photographs [excluding ultrasound and positron emission tomography (PET)]
10. Adequate bone marrow reserve white cell count (WCC) > 3.0x109/L, absolute neutrophil count (ANC) > 1.5x109/L, platelets (PLTs) > 100x109/L, haemoglobin (Hb) >10gr/dL
11. Normal liver function defined by a bilirubin < 1.25 x upper limit of normal (ULN) and transaminases < 3 x ULN,
12. Life expectancy > 6 months
13. One line of chemotherapy for metastatic disease is allowed provided this was not the last treatment received prior to study entry
14. No peripheral neuropathy > grade 1
15. No other life-threatening disease

Participant type


Age group




Target number of participants

28 patients (14 patients in each stratum)

Participant exclusion criteria

1. Non-measurable disease as sole disease sites as defined by RECIST
2. More than one line of chemotherapy for metastatic disease
3. Radiotherapy within two weeks prior to study entry
4. Surgery within two weeks prior to study entry
5. Other invasive cancer diagnosis within 5 years prior to study entry
6. Severe cardiovascular disease including myocardial infarction within 6 months of
enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease or cardiac amyloidosis
7. Uncontrolled diabetes mellitus, (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug)
8. Pregnant or breast feeding
9. Neuropathy > or = grade II
10. Has known or suspected hypersensitivity or intolerance to boron, mannitol or heparin, if an indwelling catheter is used
11. Serious medical or psychiatric conditions that precludes participation in this study

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Oncology Centre

Sponsor information


St. Augustinus Hospital, Oncology Centre (Belgium)

Sponsor details

St. Augustinus Hospital
Oncology Centre
Oosterveldlaan 24

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

St. Augustinus Hospital (Belgium)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes