Metastatic Breast CancerPhase 3TURANDOTNCT00600340
2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab
A Phase 3 study testing Bevacizumab and Paclitaxel and Bevacizumab and Capecitabine in people with Metastatic Breast Cancer, run by Central European Cooperative Oncology Group at 55 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Bevacizumab and Paclitaxel and Bevacizumab and Capecitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 564 participants
- Where
- 55 sitesin 12 countries
- Study dates
- Apr 2008to Dec 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level).
- Adequate liver function
- Total bilirubin ≤ 1.25 x upper normal limit (ULN)
- Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) < 2.5 x ULN in patients without liver metastases; < 5.0 x ULN in patients with liver metastases.
- Adequate renal function
- Serum creatinine ≤ 1.25 x ULN or calculated creatinine clearance ≥ 50 mL/min.
- Urine dipstick for proteinuria < +2. Patients discovered to have ≥ +2 proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours
- The use of full-dose oral or parenteral anticoagulants is permitted as long as the patient has been on a stable level of anticoagulation for at least two weeks at the time of randomization
- Patients on heparin treatment should have a baseline activated partial thromboplastin time (aPTT) between 1.5 - 2.5 times ULN or patients value before starting heparin treatment
- Patients on low molecular weight heparins (LMWH) should receive daily dose of 1.5 - 2 mg/kg (of enoxaparin) or appropriate doses of the correspondent anticoagulant, according to package insert
- Patients on coumarin derivatives should have an international normalized ratio (INR) between 2.0 and 3.0 assessed at baseline in two consecutive measurements 1-4 days apart
- Patients not receiving anticoagulant medication must have an INR ≤ 1.5 and aPTT ≤ 1.5 times ULN within 7 days prior to randomization
Who cannot join
- 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.
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- 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.
- History of abdominal fistula, or any grade 4 non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of randomization.
- Active infection requiring i.v. antibiotics at randomization.
- Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start.
- Women of childbearing potential (< 2 years after the last menstruation) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of study drug.
- Men who do not agree to use effective contraception during the study and for a period of 6 months following the last administration of study drug.
- Current or recent (within 28 days of randomization) treatment with another investigational drug or participation in another investigational study
- Clinically significant malabsorption syndrome or inability to take oral medication.
- Psychiatric disability judged by the Investigator to be interfering with compliance for oral drug intake.
- Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.
- Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect patient compliance with study routines, or places the patient at high risk from treatment related complications.
- Known Dihydropyrimidine Dehydrogenase (DPD) deficiency or prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency)
- Known hypersensitivity to any of the study drugs (including 5-FU) or excipients. Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. History of hypersensitivity reactions with drugs formulated in Cremophor® EL (polyoxyethylated castor oil), or previous therapy with bevacizumab.
Trial locations and contacts
55 sites in 12 countries.
55 sites in 12 countries
Poland9 sites
Wojewodzkie Centrum Onkologii
Gdansk, 80-210
Medical University of Gdansk
Gdansk, 80-211
Klinika Onkologii CMuJ
Krakow, 31-501
Lodz Oncology Center
Lodz, 93-503
Centrum Medyczne Poradnia Onkologiczna
Rzeszów, 35-021
Wojewodzki Szpital Specialistyczny
Siedlce, 08-110
Szpital Wojewodzki im Sw. Lukasza
Tarnów, 33-100
Memorial Cancer Center and Institute
Warsaw, 02-781
Dolnoslaskie Centrum Onkologii
Wroclaw, 53-413
Austria8 sites
LKH Leoben
Leoben, 8700
Hospital Barmherzige Schwestern
Linz, 4010
AKH Linz, Dep. of Oncology
Linz, 4020
Hospital Elisabethinen Linz
Linz, 4020
Univ. Klinik, Medicine III
Salzburg, 5020
2. Med. Abteilung - LKH-Steyr
Steyr, 4400
General Hospital, Medical University of Vienna
Vienna, 1090
Hospital Hietzing
Vienna, 1130
Romania6 sites
Emergency University Bucharest Hospital
Bucharest
Institutul Oncologic Bucuresti
Bucharest
Cancer Institute "I. Chiricuta"
Cluj-Napoca, 400015
University Hospital St. Spiridon Iasi
Iași, 700111
Clinical County Hospital Sibiu
Sibiu, 550003
Oncomed-Oncology Practice
Timișoara, 300239
Croatia5 sites
Department for Oncology, GH Osijek
Osijek, 31000
General Hospital Pula
Pula, 52100
University Hospital Centre Rijeka
Rijeka, 51000
University Hospital for Tumors
Zagreb
University Hospital Rebro
Zagreb
Israel5 sites
Meir Medical Center
Kfar Saba
Rabin Medical Center
Petah Tikva
Assuta Medical Center
Tel Aviv
Tel Aviv Sourasky Medical Center, Div of Oncology
Tel Aviv
Sheba Medical Center
Tel HaShomer
Czechia4 sites
Krajska nemocnice Liberec
Liberec, 460 63
Institut onkologie a rehablilitace na Plesi
Nová Ves pod Pleší
Fakultni nemocnice Olomouc
Olomouc, 77520
Charles University Prague, Dep of Oncology
Prague
Hungary4 sites
Semmelweis Univ. Radiology Clinic
Budapest, 1082
National Institute of Oncology
Budapest, 1122
Onkotherápiás Klinika,
Szeged
Markusovszky Teaching Hospital
Szombathely, 9700
Serbia4 sites
Institute for Oncology and Radiology
Belgrade, 11000
Clinical Hospital Center " Bezanijska Kosa"
Belgrade, 11080
Institute of Oncology
Kamenitz, 21204
Clinic of Oncology
Niš, 18000
Slovakia4 sites
Nomocnica Sv. Alzbety, Narodny Onkologicky Ustav
Bratislava, 81250
National Cancer Institute
Bratislava, 83310
Oncology Institute, Department of Radiotherapy and Onclogy
Košice, 04191
POKO Porad, s.r.o
Poprad, 05801
Bulgaria3 sites
Cancer Center Plovdiv
Plovdiv, 4000
University Hospital "Queen Joanna"
Sofia, 1527
Interdistrict Oncology Dispensary
Varna
Latvia2 sites
P. Stradins University Hospital
Riga, 1020
Riga Eastern Hospital - the latvian Center of Oncology
Riga, 1079
Bosnia and Herzegovina1 site
Institute of Oncology Sarajevo
Sarajevo
About this study
Official title: A Randomized Phase III 2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab for the First-line Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Locally Recurrent or Metastatic Breast Cancer
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.
Read the detailed description
Arm A:
Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks
Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks
Arm B:
Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks
Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
In both arms treatment will be given until first disease progression (PD), unacceptable toxicity or withdrawal of patient consent.
For patients who stop chemotherapy for any reason before PD (e.g. toxicity) the other treatment should be given as monotherapy until PD.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Bevacizumab and Paclitaxel, Bevacizumab and Capecitabine
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab and PaclitaxelBiological
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
Bevacizumab and CapecitabineBiological
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
| Study group | Role | What they receive |
|---|---|---|
| A Bev+Pac | Active comparator | Bevacizumab plus Paclitaxel Receives: Biological: Bevacizumab and Paclitaxel |
| B Bev+Cap | Active comparator | Bevacizumab plus Capecitabine Receives: Biological: Bevacizumab and Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Median observation time estimated with reverse Kaplan-Meier methods. Observation time (in months) is defined as time from randomization to the day the patient was last confirmed to be alive. In case of patient deaths the time was censored at the day of death.
Measured: Up to approximately 6 years
Best Overall Response (ITT Population)
The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Measured: 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)
The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Measured: 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)
The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Measured: 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)
The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Measured: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Objective Response Rate and Disease Control Rate (ITT Population)
Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Measured: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Objective Response Rate and Disease Control Rate (PP Population)
Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Measured: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Unconfirmed Objective Response Rate and Disease Control Rate (ITT Population)
Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Measured: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Unconfirmed Objective Response Rate and Disease Control Rate (PP Population)
Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment
Measured: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Progression Free Survival (ITT Population)
Progression Free Survival (PFS) is defined as time from randomization to date of documented progression or date of death due to any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients who were randomized and had no post-baseline tumor assessment were censored on the day of randomization. Median PFS, associated stratified Hazard Ratio (HR).
Measured: Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.
Progression Free Survival (PP Population)
Progression Free Survival (PFS) is defined as time from randomization to date of documented progression or date of death due to any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients who were randomized and had no post-baseline tumor assessment were censored on the day of randomization. Median PFS, associated stratified Hazard Ratio (HR).
Measured: Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.
Time to Treatment Failure (ITT Population)
Time to treatment failure (TTF) was defined as time from first drug intake to progression, death or withdrawal from study treatment, whichever occurred first. Patients without an event were censored at the date of the last tumor assessment or last treatment administration, whichever occurred last. Median TTF, associated stratified Hazard Ratio (HR).
Measured: From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years
Time to Treatment Failure (PP Population)
Time to treatment failure (TTF) was defined as time from first drug intake to progression, death or withdrawal from study treatment, whichever occurred first. Patients without an event were censored at the date of the last tumor assessment or last treatment administration, whichever occurred last. Median TTF, associated stratified Hazard Ratio (HR).
Measured: From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years
Time to Response (ITT Population)
Time to response (TR) was defined as time from randomization until occurrence of response (complete response (CR) or partial response (PR)) according to RECIST criteria. Patients without response were censored after the longest time to response observed in any patient. Median TR, associated stratified Hazard Ratio (HR). Since the median TR was not observed, the number of subjects with a response at given timepoints were reported.
Measured: Time from randomization until occurrence of response, assessed up 1.7 years
Time to Response (PP Population)
Time to response (TR) was defined as time from randomization until occurrence of response (complete response (CR) or partial response (PR)) according to RECIST criteria. Patients without response were censored after the longest time to response observed in any patient. Median TR, associated stratified Hazard Ratio (HR). Since the median TR was not observed, the number of subjects with a response at given timepoints were reported.
Measured: Time from randomization until occurrence of response, assessed up 1.7 years
Duration of Response (ITT Population)
Duration of response (DR) was defined as time from date of first occurrence of any response (complete response (CR) or partial response (PR)) until the occurrence of progression of disease or death. Patients with response who neither progressed nor died were censored at the date of their last tumor assessment. Median DR, associated stratified Hazard Ratio (HR).
Measured: Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.
Duration of Response (PP Population)
Duration of response (DR) was defined as time from date of first occurrence of any response (complete response (CR) or partial response (PR)) until the occurrence of progression of disease or death. Patients with response who neither progressed nor died were censored at the date of their last tumor assessment. Median DR, associated stratified Hazard Ratio (HR).
Measured: Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2008 (estimated)
- Study startApr 2008
- Primary completionSep 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 564 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central European Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christoph C Zielinski, MD, Principal investigator, Dep. of Internal Medicin I, Oncology, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00600340
- Sponsor's protocol ID
- CECOG/BC1.3.005
- Acronym
- TURANDOT
- Status last verified
- Oct 2019
- First submitted
- 14 Jan 2008
- Last updated
- 30 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 34037241Zielinski 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.
PubMed 27501767Brodowicz 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.
PubMed 25268370Lang 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.
PubMed 23312888
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III 2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab for the First-line Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Locally Recurrent or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00600340
- Acronym / sponsor ID
- TURANDOT / CECOG/BC1.3.005
- Conditions
- Metastatic Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 564 participants (actual)
- Lead sponsor
- Central European Cooperative Oncology GroupUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Sep 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 25 Jan 2008 (estimated)
- Results
- Posted 30 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Arm A:
Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks
Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks
Arm B:
Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks
Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
In both arms treatment will be given until first disease progression (PD), unacceptable toxicity or withdrawal of patient consent.
For patients who stop chemotherapy for any reason before PD (e.g. toxicity) the other treatment should be given as monotherapy until PD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A Bev+Pac | Active comparator | Biological: Bevacizumab and PaclitaxelBevacizumab plus Paclitaxel |
| B Bev+Cap | Active comparator | Biological: Bevacizumab and CapecitabineBevacizumab plus Capecitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab and PaclitaxelA: 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 | Biological | A Bev+Pac |
| Bevacizumab and CapecitabineB:Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks Capecitabine twice-daily 1000 mg/m², day 1 to 14, every 3 weeks | Biological | B Bev+Cap |
Primary outcome
Overall Survival (PP Population)
Time frame: 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 (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.
Overall Survival (ITT Population)
Time frame: 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 (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.
17 secondary outcomes
Observation Time (ITT Population)
Time frame: Up to approximately 6 years
Best Overall Response (ITT Population)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Objective Response Rate and Disease Control Rate (ITT Population)
Time frame: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Objective Response Rate and Disease Control Rate (PP Population)
Time frame: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Unconfirmed Objective Response Rate and Disease Control Rate (ITT Population)
Time frame: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Unconfirmed Objective Response Rate and Disease Control Rate (PP Population)
Time frame: Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.
Progression Free Survival (ITT Population)
Time frame: Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.
Progression Free Survival (PP Population)
Time frame: Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.
Time to Treatment Failure (ITT Population)
Time frame: From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years
Time to Treatment Failure (PP Population)
Time frame: From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years
Time to Response (ITT Population)
Time frame: Time from randomization until occurrence of response, assessed up 1.7 years
Time to Response (PP Population)
Time frame: Time from randomization until occurrence of response, assessed up 1.7 years
Duration of Response (ITT Population)
Time frame: Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.
Duration of Response (PP Population)
Time frame: Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34037241Hoon 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.
- Derived from this study: PubMed 27501767Zielinski 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.
- Derived from this study: PubMed 25268370Brodowicz 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.
- Derived from this study: PubMed 23312888Lang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christoph C Zielinski, MD principal investigator
Dep. of Internal Medicin I, Oncology, Medical University of Vienna
55 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bevacizumab and Paclitaxel and Bevacizumab and Capecitabine in people with Metastatic Breast Cancer, run by Central European Cooperative Oncology Group at 55 sites in 12 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 28 inclusion and 27 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 30 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in Poland, Austria, Romania, Croatia, Israel and 7 more countries. 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 30 Dec 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?
Overall Survival (PP Population) (time frame: Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years). The study lists 2 primary outcomes in all. 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 NCT00600340, which also lists 4 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 30 Dec 2019.