2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab

NCT00600340 | Completed Phase 3 Results DMC

• 1 other identifier: CECOG/BC1.3.005
• Study Type: interventional
• Target: 564
• Locations: 12 countries
• Sites: 55

Brief Summary

First-line treatment of patients with locally recurrent or metastatic, HER2-negative breast cancer who have not received prior chemotherapy for locally recurrent or metastatic disease.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Survival (PP Population)

  Overall survival (OS) defined as time from randomization to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. OS was analyzed at two looks, one interim look and the final analysis. Due to group sequential testing, the overall significance level alpha = 0.025 was spent on both looks according to Lan-DeMets spending method with O'Brien-Fleming-type boundaries. Alpha spent at Interim after 47% of information was 0.0010. Alpha spent at final analysis after 99% of information was 0.0250.

  Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years

• Overall Survival (ITT Population)

  Overall survival (OS) defined as time from randomization to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. OS was analyzed at two looks, one interim look and the final analysis. Due to group sequential testing, the overall significance level alpha = 0.025 was spent on both looks according to Lan-DeMets spending method with O'Brien-Fleming-type boundaries. Alpha spent at Interim after 50% of information was 0.0014. Alpha spent at final analysis after 99% of information was 0.0250.

  Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years

Secondary Outcomes (17)

• Observation Time (ITT Population)

  Up to approximately 6 years

• Best Overall Response (ITT Population)

  Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

• Best Overall Response (PP Population)

  Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

• Unconfirmed Best Overall Response (ITT Population)

  Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

• Unconfirmed Best Overall Response (PP Population)

  Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Study Arms (2)

A Bev+Pac

ACTIVE COMPARATOR

Bevacizumab plus Paclitaxel

Biological: Bevacizumab and Paclitaxel

B Bev+Cap

ACTIVE COMPARATOR

Bevacizumab plus Capecitabine

Biological: Bevacizumab and Capecitabine

Interventions

Bevacizumab and Paclitaxel BIOLOGICAL

A: Bevacizumab 10 mg/kg i.v., days 1 and 15, every 4 weeks Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks

A Bev+Pac

Bevacizumab and Capecitabine BIOLOGICAL

B:Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks Capecitabine twice-daily 1000 mg/m², day 1 to 14, every 3 weeks

B Bev+Cap

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained prior to any study-specific procedure.
• Age ≥18 years.
• Able to comply with the protocol.
• Histologically or cytologically confirmed, HER2-negative, adenocarcinoma of the breast with measurable or non-measurable locally recurrent or metastatic disease, who are candidates for chemotherapy. Locally recurrent disease must not be amenable to radiotherapy or resection with curative intent.
• Eastern Cooperative Oncology Group (ECOG) performance Status (PS) of 0-2.
• Life expectancy more than 12 weeks.
• Prior (neo)adjuvant chemotherapy is allowed provided that the last dose of chemotherapy was more than 6 months prior to randomization. However, if (neo)adjuvant chemotherapy was:
• Taxane-based, patients are eligible only if they received their last taxane more than 12 months prior to randomization.
• Anthracycline-based, the maximum cumulative dose of prior anthracycline therapy must not exceed 360 mg/m2 for doxorubicin and 720 mg/m2 for epirubicin.
• Prior adjuvant radiotherapy is allowed as part of the treatment of early breast cancer provided that last fraction of radiotherapy occurred at least 6 months prior to randomization. Radiotherapy administered solely for the relief of metastatic bone pain is allowed prior to study entry, providing that:
• no more than 30% of marrow-bearing bone was irradiated
• the last fraction of radiotherapy was administered ≥ 3 weeks prior to randomization.
• Adequate left ventricular ejection function (LVEF) at baseline, defined as LVEF ≥ 50% by either echocardiogram or multigated acquisition scan (MUGA).
• Adequate hematological function
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

You may not qualify if:

• Previous chemotherapy for metastatic or locally recurrent breast cancer.
• Concomitant hormonal therapy for locally recurrent or metastatic disease. Note: previous hormonal therapy is allowed for adjuvant, locally recurrent or metastatic breast cancer, but must have been discontinued at least 3 weeks prior to randomization.
• Previous radiotherapy for the treatment of metastatic disease (unless given for the relief of metastatic bone pain and with the precautions mentioned above).
• Other primary tumors within the last 5 years, except for adequately controlled limited basal cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Pre-existing peripheral neuropathy NCI CTCAE grade \> 2 at randomization.
• Evidence of spinal cord compression or current evidence of central nervous system (CNS) metastases (even if previously treated). If suspected, the patient should be scanned by CT or magnetic resonance imaging (MRI) within 28 days prior to randomization to rule out spinal / CNS metastases.
• History or evidence upon physical/neurological examination of CNS disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study treatment.
• Minor surgical procedures, including insertion of an indwelling catheter, within 24 hours prior to randomization.
• Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (\> 325 mg/day) or clopidogrel (\> 75 mg/day).
• Chronic daily treatment with corticosteroids (dose of \> 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Uncontrolled hypertension (systolic \> 150 mmHg and/or diastolic \> 100 mmHg).
• Clinically significant (i.e. active) cardiovascular disease, requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication.
• Non-healing wound, active peptic ulcer or bone fracture.

Sponsors & Collaborators

• Central European Cooperative Oncology Group: lead

Study Sites (55)

LKH Leoben

Leoben, 8700, Austria

Location

Hospital Barmherzige Schwestern

Linz, 4010, Austria

Location

AKH Linz, Dep. of Oncology

Linz, 4020, Austria

Location

Hospital Elisabethinen Linz

Linz, 4020, Austria

Location

Univ. Klinik, Medicine III

Salzburg, 5020, Austria

Location

2. Med. Abteilung - LKH-Steyr

Steyr, 4400, Austria

Location

General Hospital, Medical University of Vienna

Vienna, 1090, Austria

Location

Hospital Hietzing

Vienna, 1130, Austria

Location

Institute of Oncology Sarajevo

Sarajevo, Bosnia and Herzegovina

Location

Cancer Center Plovdiv

Plovdiv, 4000, Bulgaria

Location

University Hospital "Queen Joanna"

Sofia, 1527, Bulgaria

Location

Interdistrict Oncology Dispensary

Varna, Bulgaria

Location

Department for Oncology, GH Osijek

Osijek, 31000, Croatia

Location

General Hospital Pula

Pula, 52100, Croatia

Location

University Hospital Centre Rijeka

Rijeka, 51000, Croatia

Location

University Hospital for Tumors

Zagreb, Croatia

Location

University Hospital Rebro

Zagreb, Croatia

Location

Krajska nemocnice Liberec

Liberec, 460 63, Czechia

Location

Institut onkologie a rehablilitace na Plesi

Nová Ves pod Pleší, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 77520, Czechia

Location

Charles University Prague, Dep of Oncology

Prague, Czechia

Location

Semmelweis Univ. Radiology Clinic

Budapest, 1082, Hungary

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

Onkotherápiás Klinika,

Szeged, Hungary

Location

Markusovszky Teaching Hospital

Szombathely, 9700, Hungary

Location

Meir Medical Center

Kfar Saba, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Assuta Medical Center

Tel Aviv, Israel

Location

Tel Aviv Sourasky Medical Center, Div of Oncology

Tel Aviv, Israel

Location

Sheba Medical Center

Tel Litwinsky, Israel

Location

P. Stradins University Hospital

Riga, 1020, Latvia

Location

Riga Eastern Hospital - the latvian Center of Oncology

Riga, 1079, Latvia

Location

Wojewodzkie Centrum Onkologii

Gdansk, 80-210, Poland

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

Klinika Onkologii CMuJ

Krakow, 31-501, Poland

Location

Lodz Oncology Center

Lodz, 93-503, Poland

Location

Centrum Medyczne Poradnia Onkologiczna

Rzeszów, 35-021, Poland

Location

Wojewodzki Szpital Specialistyczny

Siedlce, 08-110, Poland

Location

Szpital Wojewodzki im Sw. Lukasza

Tarnów, 33-100, Poland

Location

Memorial Cancer Center and Institute

Warsaw, 02-781, Poland

Location

Dolnoslaskie Centrum Onkologii

Wroclaw, 53-413, Poland

Location

Emergency University Bucharest Hospital

Bucharest, Romania

Location

Institutul Oncologic Bucuresti

Bucharest, Romania

Location

Cancer Institute "I. Chiricuta"

Cluj-Napoca, 400015, Romania

Location

University Hospital St. Spiridon Iasi

Iași, 700111, Romania

Location

Clinical County Hospital Sibiu

Sibiu, 550003, Romania

Location

Oncomed-Oncology Practice

Timișoara, 300239, Romania

Location

Institute for Oncology and Radiology

Belgrade, 11000, Serbia

Location

Clinical Hospital Center " Bezanijska Kosa"

Belgrade, 11080, Serbia

Location

Institute of Oncology

Kamenitz, 21204, Serbia

Location

Clinic of Oncology

Niš, 18000, Serbia

Location

Nomocnica Sv. Alzbety, Narodny Onkologicky Ustav

Bratislava, 81250, Slovakia

Location

National Cancer Institute

Bratislava, 83310, Slovakia

Location

Oncology Institute, Department of Radiotherapy and Onclogy

Košice, 04191, Slovakia

Location

POKO Porad, s.r.o

Poprad, 05801, Slovakia

Location

Related Publications (4)

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

• Zielinski C, Lang I, Inbar M, Kahan Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. doi: 10.1016/S1470-2045(16)30154-1. Epub 2016 Aug 5.

  PMID: 27501767 DERIVED

• Brodowicz T, Lang I, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Petruzelka L, Eniu A, Anghel R, Koynov K, Vrbanec D, Pienkowski T, Melichar B, Spanik S, Ahlers S, Messinger D, Inbar MJ, Zielinski C. Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses. Br J Cancer. 2014 Nov 25;111(11):2051-7. doi: 10.1038/bjc.2014.504. Epub 2014 Sep 30.

  PMID: 25268370 DERIVED

• Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. doi: 10.1016/S1470-2045(12)70566-1. Epub 2013 Jan 10.

  PMID: 23312888 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Paclitaxel; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: MD. Christiane Thallinger
• Organization: CECOG

office@cecog.at

+43 1 409 77 25

Study Officials

• Christoph C Zielinski, MD

  Dep. of Internal Medicin I, Oncology, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: 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: January 14, 2008
• First Posted: January 25, 2008
• Study Start: April 1, 2008
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 30, 2019
• Results First Posted: December 30, 2019

Record last verified: 2019-10

Locations

RO (6); SE (4); BU (3); SL (4); CZ (4); AU (8); BO (1); HU (4); CR (5); PL (9); IL (5); LA (2)