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

NCT00545077 | Completed Phase 3 Results DMC

• 2 other identifiers: GEICAM/2006-11/GBG 512007-002841-19
• Study Type: interventional
• Target: 380
• Locations: 2 countries
• Sites: 70

Brief 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.

Conditions

Breast Cancer

Keywords

endocrine therapy; bevacizumab; breast cancer; first-line therapy

Outcome Measures

Primary Outcomes (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.

  Up to 2 years

Secondary Outcomes (5)

• Overall Survival (OS)

  Up to 2 years

• Time to Treatment Failure (TTF)

  Up to 2 years

• Overall Response Rate (ORR)

  2 years

• Response Duration (RD)

  Up to 2 years

• Clinical Benefit Rate (CBR)

  Up to 2 years

Study Arms (2)

Arm A: Endocrine Therapy (ET)

ACTIVE COMPARATOR

Endocrine 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.

Drug: Letrozole; Drug: Fulvestrant

Arm B: ET with Bevacizumab (ET-B)

EXPERIMENTAL

Endocrine 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.

Drug: Letrozole; Drug: Bevacizumab; Drug: Fulvestrant

Interventions

Letrozole DRUG

Also known as: Femara

Arm A: Endocrine Therapy (ET); Arm B: ET with Bevacizumab (ET-B)

Bevacizumab DRUG

Also known as: Avastin

Arm B: ET with Bevacizumab (ET-B)

Fulvestrant DRUG

Also known as: Faslodex

Arm A: Endocrine Therapy (ET); Arm B: ET with Bevacizumab (ET-B)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Hoffmann-La Roche: collaborator
• GBG Forschungs GmbH: collaborator

Study Sites (70)

Klinikum Bayreuth

Bayreuth, 95445, Germany

Location

Universitätsklinikum Charité

Berlin, 10117, Germany

Location

Praxisklinik

Berlin, 10367, Germany

Location

Praxis Dr. med. W. Schoenegg

Berlin, 10719, Germany

Location

Johanniter Krankenhaus

Bonn, 53113, Germany

Location

Klinikum Sindelfingen-Böblingen / Kliniken Böblingen

Böblingen, 71032, Germany

Location

Onkologische Schwerpunktpraxis

Bremen, 28203, Germany

Location

St. Elisabeth-KKH

Cologne, 52428, Germany

Location

Berufsausübungsgemeinschaft

Dresden, 01307, Germany

Location

Kliniken Essen-Mitte Evang. Huyssens-Stiftung/Knappschaft

Essen, 45136, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Kliniken Esslingen

Esslingen am Neckar, 73730, Germany

Location

Klinikum Fulda

Fulda, 36043, Germany

Location

Albertinen-Krankenhaus

Hamburg, 22457, Germany

Location

Kreiskrankenhaus Hameln

Hamelin, 31785, Germany

Location

Gynäkologisch-onkologische Praxis

Hanover, 30177, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Praxisklinik - Dialysezentrum - Herne

Herne, 44623, Germany

Location

St. Vincentius Kliniken Karlsruhe

Karlsruhe, 76137, Germany

Location

Onkologische Schwerpunktpraxis

Kronach, 96317, Germany

Location

Caritas Krankenhaus Lebach

Lebach, 66822, Germany

Location

St. Vincenz Krankenhaus

Limburg, 65549, Germany

Location

St. Vincenz und Elisabeth-Hospital

Mainz, 55131, Germany

Location

Universitätsklinikum

Mainz, 55131, Germany

Location

Ev. Krankenhaus Bethesda

Mönchengladbach, 41061, Germany

Location

Universitätsklinikum

Münster, 48149, Germany

Location

Frauenklinik Rheinfelden

Rheinfelden, 79618, Germany

Location

Klinikum Rosenheim

Rosenheim, 83022, Germany

Location

Onkolog. Schwerpunktpraxis

Rosenheim, 83022, Germany

Location

Gemeinschaftspraxis für Gynäkologie und Geburtshilfe

Salzgitter, 38226, Germany

Location

Krankenhaus Weinheim

Weinheim, 69469, Germany

Location

Praxis Dres. Reichert und Janssen

Westerstede, 26655, Germany

Location

St. Josefs-Hospital

Wiesbaden, 65189, Germany

Location

Dr.-Horst-Schmidt-Kliniken GmbH

Wiesbaden, 65199, Germany

Location

Marienhospital Witten

Witten, 58452, Germany

Location

Onkologische Gemeinschaftspraxis

Würselen, 52146, Germany

Location

Hospital General de Elche

Elche, Alicante, 3203, Spain

Location

Hospital Germans Trias i Pujol

Badalona, Badalona/Barcelona, 08916, Spain

Location

Hospital Son Dureta

Palma de Mallorca, Balearic Islands, 07014, Spain

Location

Instituto catalán de Oncología de Barcelona

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Xarxa Asistencial de Manresa

Manresa, Barcelona, 08243, Spain

Location

Corporación Sanitaria Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Consorci Sanitari de Terrasa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Mutua de Terrasa

Terrassa, Barcelona, 08221, Spain

Location

Hospital de Barbastro

Barbastro, Huesca, 22300, Spain

Location

Fundación Hospital de Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Hospital Universitario de Canarias

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

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Centro Oncológico de Galicia

A Coruña, 15009, Spain

Location

Hospital General de Alicante

Alicante, 03010, Spain

Location

Hospital Infanta Cristina de Badajoz

Badajoz, 06080, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Provincial de Córdoba

Córdoba, 14004, Spain

Location

Instituto Catalan de Oncologia de Girona

Girona, 17007, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Arnau de Vilanova de Lérida

Lleida, 25198, Spain

Location

Hospital Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

CIOCC Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Virgen de La Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Virgen de la Salud

Toledo, 45004, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Clinico de Valencia

Valencia, 46010, Spain

Location

Hospital Clinico Universitario Valencia

Valencia, 46010, Spain

Location

Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (3)

• 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.

  PMID: 25691671 RESULT

• 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.

  PMID: 31276981 RESULT

• 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.

  PMID: 34218359 RESULT

Related Links

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Bevacizumab; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Scientific Director / Medical Lead / Project Manager
• Organization: Spanish Breast Cancer Research Group

geicam@geicam.org

+34916592870

Study Officials

• Study Director

  GBG Forschungs GmbH

  STUDY DIRECTOR

• Study Director

  Hospital San Carlos, Madrid

  STUDY DIRECTOR

• Study Director

  Hospital Provincial de Córdoba

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 17, 2007
• Study Start: November 6, 2007
• Primary Completion: December 1, 2013
• Study Completion: July 24, 2014
• Last Updated: March 31, 2023
• Results First Posted: July 10, 2019

Record last verified: 2023-03

Locations

ES (34); DE (36)