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AzTrials

Breast CancerPhase 3NCT00545077

Bevacizumab + Endocrine Treatment vs Endocrine Treatment as First Line in Postmenopausal Women

A Phase 3 study testing Letrozole, Bevacizumab and Fulvestrant in people with Breast Cancer, run by Spanish Breast Cancer Research Group at 70 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Locally advanced or metastatic breast cancer in postmenopausal women with negative Human Epidermal Growth Factor Receptor 2 (HER2), who are candidates for hormone treatment and who have not received previous chemotherapy or hormonotherapy for the metastatic disease. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Letrozole, Bevacizumab and Fulvestrant
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
380 participants
Where
70 sitesin 2 countries
Study dates
6 Nov 2007to 24 Jul 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Before starting the specific protocol procedures, the written informed consent must be obtained and documented.
  • Women ≥ 18 years.
  • Capacity to comply with all the protocol requirements.
  • Functional Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
  • Life expectancy ≥ 24 weeks.
  • Histologically confirmed breast adenocarcinoma, with measurable or non-measurable, locally advanced or metastatic (stage IV) disease. In the event that the patient only has locally advanced disease, she will not be able to undergo curative local treatment. Patients with metastasis confined to the bone can be chosen, but the disease must be confirmed by radiology, CT scan or Nuclear magnetic resonance (NMR) if there is any doubt after a single bone scan.
Show all 17Show fewer
  • Patients with HER2-negative disease evaluated by Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH)/Chromogenic in situ hybridisation (CISH) (IHC 0 or 1+, or 2+ and negative FISH). Patients with 3+ by IHC cannot be chosen regardless of the FISH/CISH status and those with positive FISH/CISH (> 2 amplifications) cannot be chosen either, regardless of the IHC findings.
  • Positive hormone receptors (estrogen receptor [ER] and/or progesterone receptor [PgR]) evaluated by a local or central laboratory, according to the criteria of the participating institution.
  • Patients who are candidates for receiving first-line treatment with letrozole.
  • Patients may have received (neo)adjuvant chemotherapy, provided that the last dose of the latter was received at least 12 months before randomization. Patients must be recovered from toxicity.
  • The patients are allowed to have received adjuvant radiotherapy, provided that it was completed at least 6 weeks before randomization and the patient has recovered from the reversible acute effects of the radiation. The previous administration of radiotherapy to palliate the pain of bone metastases is authorized, provided that:
  • Not more than 30% of bone marrow has been irradiated.
  • The patient has recovered from the reversible acute effects of the radiation.
  • The patient has at least one metastatic location which has not been irradiated and which may be evaluated for progression, or a clear progression of the bone disease has been objectified after the end of the palliative radiotherapy.
  • The patients may have received any kind of previous (neo)adjuvant hormone therapy provided that they are considered to be candidates for first-line hormonotherapy with either letrozole or fulvestrant.
  • The treatment with bisphosphonates is allowed and recommended for patients with bone metastases. Whenever it is possible, the treatment should be started before or within the 4 weeks of starting the study therapy. The patients starting treatment with bisphosphonates must be carefully evaluated so that they do not mask the progression of the disease.
  • In the patients with heart failure risk (e.g. previously treated with > 360mg/m2 of doxorubicin or equivalent doses of other anthracyclines), the Left Ventricular Ejection Fraction (LVEF) must be determined by means of an echocardiogram or radionuclide ventriculography (MUGA), and it must t be > the lower limit of normal.

Who cannot join

  • Evolutionary disease requiring an immediate treatment with cytotoxic chemotherapy according to the investigator's judgment.
  • Patients with locally advanced breast cancer who are expected to undergo surgery or curative radiotherapy.
  • Previous chemotherapy or hormonotherapy for the metastatic disease. Patients may have received neoadjuvant chemotherapy or neoadjuvant hormonotherapy with curative intention as a part or as an alternative to an adjuvant treatment. For the previous neoadjuvant hormonotherapy the same premises than for the adjuvant hormonotherapy are valid.
  • Previous therapy with anti-vascular endothelial growth factor (VEGF) or VEGF Receptor (VEGFR) tyrosine-kinase inhibitors.
  • History of another pathology that may affect the development of the protocol or the interpretation of results. It is considered that patients who have suffered from a skin carcinoma that is not melanoma, cervical carcinoma in situ or another neoplasia treated with a curative intention and with a disease-free interval exceeding 5 years can be chosen.
  • Evidence of central nervous system (CNS) metastasis. A CT scan or brain NMR must be done within the 4 weeks before the randomization in case of suspecting brain metastasis.
Show all 26Show fewer
  • History or evidence in the physical or neurological examination of CNS pathology unrelated to cancer unless it is suitable treated with standard therapy (e.g. uncontrolled convulsions).
  • History of peripheral neuropathy National Cancer Institute (NCI) CTCAE grade >2 at the time of randomization.
  • Patients subjected to major surgical procedures, open biopsies or those having significant trauma injuries within the 28 days prior to randomization, or patients who are expected to undergo a major surgical procedure that must necessarily be performed within the course of the study.
  • Minor surgical procedures in the 7 days prior to randomization.
  • Unsuitable bone marrow supply: absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L or Hb < 10 g/dL.
  • Impaired liver function: total bilirubin total > 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) > 2.5 x ULN (> 5 x ULN in patients with liver metastases).
  • Impaired kidney function:
  • Serum creatinine > 2.0 mg/dL or 177 µmol/L.
  • Proteinuria determined by reactive strip > 2+. A 24h determination of proteins in urine will be requested for the patients with > 2+ in the baseline analysis and must have a protein figure < 1 g/24 h.
  • Chronic treatment with oral corticoids (dose > 10 mg/day of methylprednisolone or equivalent): the use of inhaled corticoids is allowed.
  • Chronic treatment with acetylsalicylic acid (> 325 mg/day) or clopidogrel (> 75 mg/day).
  • Uncontrolled arterial hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant cardiovascular disease: for example cerebrovascular accident (CVA) (in the 6 months prior to randomization), coronaropathy or history of acute mycardial infarction (AMI) in the last 6 months, unstable angina, congestive heart failure of grade > II of the New York Heart Association (NYHA) or severe heart arrhythmias which are not controlled with medication or which can potentially interfere with the study treatment.
  • History or evidence of hemorrhagic diathesis or coagulopathy with bleeding risk.
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abcess in the 6 months prior to randomization.
  • Active infection requiring i.v. antibiotics at the time of randomization.
  • Unhealed wounds, active peptic ulcer, esophageal varices.
  • Any other disease, psychological or metabolic alteration, found in the physical or laboratory examination, providing reasonable indications for suspecting a disease or complaint for which the use of any of the study drugs are contraindicated, or which may affect the patient's compliance with the routine procedures of the study or which places the patient at a high risk of experiencing complications related to the treatment.
  • Current or recent (within 30 days prior to that start of the study treatment) treatment with another drug under investigation or participation in another investigation study.
  • Known hypersensitivity to any of the study drugs or their components.
  • Hypersensitivity to the products of Chinese hamster ovary cells or to other human or humanized recombinant antibodies.

Trial locations and contacts

70 sites in 2 countries.

70 sites in 2 countries

Germany36 sites

  • Klinikum Bayreuth

    Bayreuth, 95445

  • Universitätsklinikum Charité

    Berlin, 10117

  • Praxisklinik

    Berlin, 10367

  • Praxis Dr. med. W. Schoenegg

    Berlin, 10719

  • Klinikum Sindelfingen-Böblingen / Kliniken Böblingen

    Böblingen, 71032

  • Johanniter Krankenhaus

    Bonn, 53113

  • Onkologische Schwerpunktpraxis

    Bremen, 28203

  • St. Elisabeth-KKH

    Cologne, 52428

  • Berufsausübungsgemeinschaft

    Dresden, 01307

  • Kliniken Essen-Mitte Evang. Huyssens-Stiftung/Knappschaft

    Essen, 45136

  • Universitätsklinikum Essen

    Essen, 45147

  • Kliniken Esslingen

    Esslingen am Neckar, 73730

  • Klinikum Fulda

    Fulda, 36043

  • Albertinen-Krankenhaus

    Hamburg, 22457

  • Kreiskrankenhaus Hameln

    Hamelin, 31785

  • Gynäkologisch-onkologische Praxis

    Hanover, 30177

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Praxisklinik - Dialysezentrum - Herne

    Herne, 44623

  • St. Vincentius Kliniken Karlsruhe

    Karlsruhe, 76137

  • Onkologische Schwerpunktpraxis

    Kronach, 96317

  • Caritas Krankenhaus Lebach

    Lebach, 66822

  • St. Vincenz Krankenhaus

    Limburg, 65549

  • St. Vincenz und Elisabeth-Hospital

    Mainz, 55131

  • Universitätsklinikum

    Mainz, 55131

  • Ev. Krankenhaus Bethesda

    Mönchengladbach, 41061

  • Universitätsklinikum

    Münster, 48149

  • Frauenklinik Rheinfelden

    Rheinfelden, 79618

  • Klinikum Rosenheim

    Rosenheim, 83022

  • Onkolog. Schwerpunktpraxis

    Rosenheim, 83022

  • Gemeinschaftspraxis für Gynäkologie und Geburtshilfe

    Salzgitter, 38226

  • Krankenhaus Weinheim

    Weinheim, 69469

  • Praxis Dres. Reichert und Janssen

    Westerstede, 26655

  • St. Josefs-Hospital

    Wiesbaden, 65189

  • Dr.-Horst-Schmidt-Kliniken GmbH

    Wiesbaden, 65199

  • Marienhospital Witten

    Witten, 58452

  • Onkologische Gemeinschaftspraxis

    Würselen, 52146

Other trials in Germany

Spain34 sites

  • Complejo Hospitalario Universitario A Coruña

    A Coruña, 15006

  • Centro Oncológico de Galicia

    A Coruña, 15009

  • Fundación Hospital de Alcorcón

    Alcorcón, Madrid, 28922

  • Hospital General de Alicante

    Alicante, 03010

  • Hospital Infanta Cristina de Badajoz

    Badajoz, 06080

  • Hospital Germans Trias i Pujol

    Badalona, Badalona/Barcelona, 08916

  • Hospital de Barbastro

    Barbastro, Huesca, 22300

  • Hospital del Mar

    Barcelona, 08003

  • Hospital Clinic i Provincial

    Barcelona, 08036

  • Hospital Provincial de Córdoba

    Córdoba, 14004

  • Hospital General de Elche

    Elche, Alicante, 3203

  • Instituto Catalan de Oncologia de Girona

    Girona, 17007

  • Complejo Hospitalario de Jaén

    Jaén, 23007

  • Instituto catalán de Oncología de Barcelona

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Arnau de Vilanova de Lérida

    Lleida, 25198

  • Hospital Gregorio Marañon

    Madrid, 28007

  • Hospital Ramón y Cajal

    Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, 28040

  • CIOCC Clara Campal

    Madrid, 28050

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Xarxa Asistencial de Manresa

    Manresa, Barcelona, 08243

  • Hospital Son Dureta

    Palma de Mallorca, Balearic Islands, 07014

  • Corporación Sanitaria Parc Taulí

    Sabadell, Barcelona, 08208

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320

  • Hospital Virgen de La Macarena

    Seville, 41009

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Consorci Sanitari de Terrasa

    Terrassa, Barcelona, 08221

  • Hospital Mutua de Terrasa

    Terrassa, Barcelona, 08221

  • Hospital Virgen de la Salud

    Toledo, 45004

  • Hospital Universitario La Fe

    Valencia, 46009

  • Instituto Valenciano de Oncología

    Valencia, 46009

  • Hospital Clinico de Valencia

    Valencia, 46010

  • Hospital Clinico Universitario Valencia

    Valencia, 46010

  • Hospital Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: Multicenter, Randomized Trial to Evaluate Efficacy and Safety of Bevacizumab in Combination With Endocrine Treatment vs Endocrine Alone, in Postmenopausal With Advanced or Metastatic Cancer With Indication of Hormonotherapy as First-line

Locally advanced or metastatic breast cancer in postmenopausal women with negative Human Epidermal Growth Factor Receptor 2 (HER2), who are candidates for hormone treatment and who have not received previous chemotherapy or hormonotherapy for the metastatic disease.

Read the detailed description

The main endpoint of the study is progression-free survival (PFS). It has been calculated that 378 patients will need to be included, according to the following assumptions:

  • Recruitment period of 21 months.
  • Minimum follow-up period of 9 months.
  • PFS of 9 months in the control arm (letrozole in monotherapy). Using a two-sided log-rank test, for a 5% α level, 344 patients (172 in each treatment arm) will be required for 270 events to occur, which will provide an 80% power for detecting a hazard ratio of 0.69 (corresponding to a PFS median of 13 months in the bevacizumab arm). This sample size has been adjusted for an intermediate analysis when 2/3 of the total of required events have occurred. This intermediate analysis can be avoided if, at the time in which it must be carried out, it is estimated that the final analysis will be carried out in 4 months.

Taking into account a 10% percentage of losses, 378 patients are expected to be included in the study.

An intermediate safety evaluation will be carried out when 63 patients have finished their treatment in each treatment arm.

A multicenter, randomized phase III clinical trial. After verifying the selection criteria, the patients will be randomized to receive letrozole alone or in combination with bevacizumab. Before randomization, the patients will be stratified according to the following prognosis factors:

  • Estrogen Receptor (ER)+ / Progesterone Receptor (PgR)+ vs the other options (ER+/PgR- vs ER-/PgR+)
  • Previous adjuvant hormonotherapy (yes/no)
  • Status: locally advanced vs metastatic.
  • Measurable vs non measurable disease
  • Visceral disease (yes/no)
  • PFS.
Conditions
Breast Cancer
Keywords
endocrine therapy, bevacizumab, breast cancer, first-line therapy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00545077
Study groupRoleWhat they receive
Arm A: Endocrine Therapy (ET)Active comparatorEndocrine treatment consisting of either letrozole or fulvestrant. Patients will be randomized to receive bevacizumab 15mg/kg every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.
Receives: Drug: Letrozole; Drug: Fulvestrant
Arm B: ET with Bevacizumab (ET-B)ExperimentalEndocrine treatment consisting of either letrozole or fulvestrant. Patients will be randomized to receive bevacizumab 15mg/kg i.v. on day 1 every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.
Receives: Drug: Letrozole; Drug: Bevacizumab; Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    PFS was defined as the time elapsed from randomization until the date in which the progression of the disease or the death for any reason (whichever occurs first) is documented.

    Measured: Up to 2 years

Secondary outcomes (5)

  1. Overall Survival (OS)

    OS was defined as the time elapsed since randomization, until the time in which death occurs for any reason. The patients lost in the follow-up will be censured at the date of the last follow-up.

    Measured: Up to 2 years

  2. Time to Treatment Failure (TTF)

    TTF was defined as the time elapsed since randomization until the date the treatment is discontinued for any reason (progression disease, treatment toxicity or death).

    Measured: Up to 2 years

  3. Overall Response Rate (ORR)

    ORR to treatment is reflected by a frequency table containing the data of the best overall response (Complete Response, Partial Response,Stable Disease or Progressive Disease) experienced for each patient during treatment (recorded from the start of the treatment until disease progression) per arm.

    Measured: 2 years

  4. Response Duration (RD)

    RD was defined as the time elapsed from when a partial or complete response is verified until the time in which progression or death occurs.

    Measured: Up to 2 years

  5. Clinical Benefit Rate (CBR)

    CBR was defined as the percentage of patients achieving a Complete Response (CR), a Partial Response (PR) or a stabilization of the disease (SD) > 6 months: the response will be evaluated according to the RECIST criteria. In the patients without measurable disease at the baseline time, the clinical benefit will be defined as the absence of progression > 6 months.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2007 (estimated)
  2. Study start6 Nov 2007
  3. Primary completionDec 2013
  4. Study completion24 Jul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
380 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00545077
Sponsor's protocol ID
GEICAM/2006-11/GBG 51
Other IDs
2007-002841-19
Status last verified
Mar 2023
First submitted
16 Oct 2007
Last updated
31 Mar 2023
Data monitoring committee
Yes

Publications

  • Martin M, Loibl S, von Minckwitz G, Morales S, Martinez N, Guerrero A, Anton A, Aktas B, Schoenegg W, Munoz M, Garcia-Saenz JA, Gil M, Ramos M, Margeli M, Carrasco E, Liedtke C, Wachsmann G, Mehta K, De la Haba-Rodriguez JR. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol. 2015 Mar 20;33(9):1045-52. doi: 10.1200/JCO.2014.57.2388. Epub 2015 Feb 17.

    PubMed 25691671

  • Martin M, Loibl S, Hyslop T, De la Haba-Rodriguez J, Aktas B, Cirrincione CT, Mehta K, Barry WT, Morales S, Carey LA, Garcia-Saenz JA, Partridge A, Martinez-Janez N, Hahn O, Winer E, Guerrero-Zotano A, Hudis C, Casas M, Rodriguez-Martin C, Furlanetto J, Carrasco E, Dickler MN; GEICAM Spanish Breast Cancer Group; GBG (German Breast Group); Alliance for Clinical Trials in Oncology (Alliance). Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials. Eur J Cancer. 2019 Aug;117:91-98. doi: 10.1016/j.ejca.2019.06.002. Epub 2019 Jul 2.

    PubMed 31276981

  • Polley MC, Dickler MN, Sinnwell J, Tenner K, de la Haba J, Loibl S, Goetz MP, Bergh J, Roberston J, Couch F, Ellis MJ, Martin M. A clinical calculator to predict disease outcomes in women with hormone receptor-positive advanced breast cancer treated with first-line endocrine therapy. Breast Cancer Res Treat. 2021 Aug;189(1):15-23. doi: 10.1007/s10549-021-06319-z. Epub 2021 Jul 3.

    PubMed 34218359

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Letrozole, Bevacizumab and Fulvestrant in people with Breast Cancer, run by Spanish Breast Cancer Research Group at 70 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in Germany, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00545077, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2023; AzTrials last refreshed its copy on 7 Nov 2026.

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