Breast CancerPhase 3NCT01095003
Trial of Vinflunine Plus Capecitabine in Advanced Breast Cancer
A Phase 3 study testing Vinflunine plus Capecitabine and Capecitabine in people with Breast Cancer, run by Pierre Fabre Medicament at 110 sites in 21 countries.
Trial summary
The increasing use of anthracyclines and taxanes in the adjuvant, neoadjuvant and first-line metastatic settings, led to a raise of patients presenting with metastatic breast cancer after treatment with these agents. Read more about this study
- Who is it for?
- Ages 21 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Vinflunine plus Capecitabine and Capecitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 770 participants
- Where
- 110 sitesin 21 countries
- Study dates
- May 2009to Oct 2015
- 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 21 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- female patients
- 21 years of age or older
- histologically/cytologically confirmed carcinoma of the breast
- documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy
- either one, two or three prior chemotherapy regimens
- prior treatments including both an anthracycline and a taxane and patient no longer candidate for these drugs
Show all 10Show fewer
- measurable or non-measurable disease according to RECIST 1.1
- Karnofsky performance score of at least 70 %
- adequate haematological, hepatic and renal functions
- ECG without clinically relevant abnormality
Who cannot join
- known or clinical evidence of brain metastasis or leptomeningeal involvement
- pulmonary lymphangitis or symptomatic pleural effusion
- any serious, concurrent uncontrolled medical disorder
- history of second primary malignancy
- preexisting motor/sensory peripheral neuropathy
- known history of HIV infection
Show all 10Show fewer
- prior therapy with capecitabine and/or vinca-alkaloids
- history of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or contra indication to any of these drugs
- known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
- pregnancy or breast feeding
Trial locations and contacts
110 sites in 21 countries.
110 sites in 21 countries
France13 sites
Study site
Angers
Study site
Caen
Study site
Dijon
Study site
Le Mans
Study site
Lorient
Study site
Lyon
Study site
Montpellier
Study site
Nantes
Study site
Saint-Brieuc
Study site
Saint-Cloud
Study site
Saint-Herblain
Study site
Tours
Study site
Villejuif
Russia11 sites
Study site
Arkhangelsk
Study site
Chelyabinsk
Study site
Moscow
Study site
Ryazan
Study site
Saint Petersburg
Study site
Saratov
Study site
Stavropol
Study site
Tambov
Study site
Ufa
Study site
Vladimir
Study site
Volgograd
India10 sites
Study site
Bangalore
Study site
Bhopal
Study site
Calicut
Study site
Chhatrapati Sambhajinagar
Study site
Jaipur
Study site
Kolkata
Study site
Mumbai
Study site
Patna
Study site
Pune
Study site
Trivandrum
Italy10 sites
Study site
Avellino
Study site
Cagliari
Study site
Cremona
Study site
Fabriano
Study site
Milan
Study site
Monza
Study site
Padova
Study site
Pisa
Study site
Rozzano
Study site
Verona
United Kingdom10 sites
Study site
Belfast
Study site
Chelmsford
Study site
Keighley
Study site
London
Study site
Nottingham
Study site
Peterborough
Study site
Portsmouth
Study site
Sheffield
Study site
Southend-on-Sea
Study site
Sutton
Poland6 sites
Study site
Bialystok
Study site
Gdansk
Study site
Krakow
Study site
Lodz
Study site
Lubin
Study site
Warsaw
Ukraine6 sites
Study site
Cherkasy
Study site
Dnipropetrovsk
Study site
Donetsk
Study site
Khmelnytskyi
Study site
Kyiv
Study site
Simferopol
Argentina5 sites
Study site
Buenos Aires
Study site
Quilmes
Study site
Rosario
Study site
San Martin
Study site
San Miguel de Tucumán
Spain5 sites
Study site
Barcelona
Study site
Lleida
Study site
Madrid
Study site
Oviedo
Study site
Valencia
Belarus4 sites
Study site
Grodno
Study site
Homyel
Study site
Minsk
Study site
Vitebsk
Brazil4 sites
Study site
Curitiba
Study site
Porto Alegre
Study site
Santo André
Study site
São Paulo
Mexico4 sites
Study site
Chihuahua City
Study site
León
Study site
Mexico City
Study site
Saltillo
South Africa4 sites
Study site
Durban
Study site
Kimberley
Study site
Pretoria
Study site
Sandton
Switzerland3 sites
Study site
Genolier
Study site
Lausanne
Study site
Winterthur
About this study
Official title: A Phase III Trial of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant.
The increasing use of anthracyclines and taxanes in the adjuvant, neoadjuvant and first-line metastatic settings, led to a raise of patients presenting with metastatic breast cancer after treatment with these agents. Options for the treatment of patients who have progressed after an anthracycline and a taxane are limited. The high level of in-vitro synergy of vinflunine combined with 5-fluorouracil (5-FU) together with the good tolerance and the encouraging response rate observed while combining IV vinflunine to oral capecitabine make it a promising combination to investigate further in a phase III trial. This phase III trial will evaluate the effectiveness and the safety profile of such combination for the treatment of patient with advanced breast cancer previously treated with or resistant to anthracycline and taxane resistant.
Read the detailed description
This multicentre, open-label, randomised, Phase III study will enrol 764 patients with advanced breast cancer who have previously been treated with or are resistant to an anthracycline and who are taxane resistant. Patients will be randomised in a 1:1 ratio to receive vinflunine plus capecitabine (Arm A) or capecitabine alone (Arm B).
Randomisation will be stratified according to a minimization procedure:
- Resistance to anthracyclines ("yes" versus "no"), Relapse ≤ 12 months in the adjuvant or neoadjuvant setting or progression ≤ 4 months in the metastatic setting,
- Karnofsky performance status ("90-100" versus "70-80"),
- Measurable disease ("yes" versus "no"),
- The number of prior lines of chemotherapy in the metastatic setting ("0" versus "1" versus "> 1") and,
- Study site.
Patients randomised in Arm A will receive:
- Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute i.v. infusion and,
- Capecitabine which will be self-administered by the patient in an outpatient setting. Patients will take 825 mg/m² twice daily per os for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest. A cycle of therapy is defined as 3 weeks.
For patients randomised in Arm B, capecitabine will be self administered by the patient in an outpatient setting. Patients will take 1250 mg/m² twice daily per os for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest. A cycle of therapy is defined as 3 weeks.
The doses and timing of treatment will be modified based on toxicities experienced by the patient.
Patients will be assessed for toxicity, tumour response and progression at regular intervals during treatment. Patients will be evaluated for safety if they received any study drug. Laboratory values, adverse events and other symptoms will be graded.
Tumour response, progression-free survival and duration of response will be evaluated for all randomised patients. Tumour assessment is to be performed every 6 weeks (+/- 3 working days) from randomisation (regardless of the timing of treatment cycles) until disease progression is documented. Patients who discontinue protocol treatment for reasons other than disease progression will have tumour assessments every 6 weeks until documented disease progression. Patients may continue to receive additional cycles of therapy until progressive disease or intolerable toxicity.
Quality of Life assessment, will be measured by EORTC QLQ-C30 and QLQ-BR23 questionnaires, which will be completed by patients.
The primary endpoint for the trial is progression free survival calculated from the date of randomization until the date of progression or the date of death whatever the reason of death. The analysis of Progression-Free Survival is planned to take place when 615 progressions or deaths have been observed. One interim safety analysis is planned and will take place when 50 patients of each arm have completed at least one cycle of study treatment. It is anticipated that up to 170 active study centres will participate, and that accrual will be completed in approximately 30 months.
- Conditions
- Breast Cancer
- Being tested
- Vinflunine plus Capecitabine, 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.
Vinflunine plus CapecitabineDrug
Also called JAVLOR, L00070 IN
Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks
Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
CapecitabineDrug
Also called XELODA
Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Vinflunine plus Capecitabine | Experimental | Patients received (in combination with capecitabine)
• Vinflunine at the dose of 280 mg/m² and as a 20-minute IV. infusion on day 1 of each cycle repeated every 3 weeks. Receives: Drug: Vinflunine plus Capecitabine |
| Capecitabine single-agent | Active comparator | Capecitabine at the dose of 825mg/m² per os twice per day each morning and each evening for 14 consecutive days beginning on day 1 of each cycle repeated every 3 weeks (self-administered). Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
PFS is defined as time from date of randomization to date of the first documentation of objective tumor progression (according to the Independent Response Review Committee (IRC) and based on RECIST version 1.1) or death due to any cause.
The PFS was primarily analysed in the Intent-to-treat (ITT) population. Patients lost to follow-up, or without a known record of progression or death at time of analysis had the progression-free survival censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression, whichever occurs last.
Measured: Baseline up to 2 years 7 months
Secondary outcomes (4)
Overall Survival
The overall survival (OS) was defined as the duration between the date of randomisation and the date of death from any cause. The OS analysis was performed in the ITT population and the eligible and per protocol populations once the required number of events (631 deaths) was observed Patients lost to follow-up, or without a known record of death at time of analysis had the OS censored at the date of last contact.
Measured: Baseline upto 3 years 10 months
Overall Response Rate (ORR)
ORR defined as documentation of complete or partial response that was subsequently confirmed to first documentation of disease progression or to death due to any cause, whichever occurred first.
Measured: Baseline upto 2 years 7 months
Disease Control Rate
Disease control rate defined (DCR) as the sum of confirmed complete response, confirmed partial response and stabilisation rate.
Measured: Baseline up to 2 years 7 months
Duration of Response
Measured from the first time that measurement criteria were first met for objective response (documented CR or PR) until recurrence/progression or death whatever the cause.
Measured: Baseline up to 2 years 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2010 (estimated)
- Study startMay 2009
- Primary completionDec 2011
- Study completionOct 2015
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 (1)Papers the sponsor has linked to this study.
- Other trials for 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
- 770 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pierre Fabre Medicament
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jean-Claude VEDOVATO, Study director, Pierre Fabre Medicament
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01095003
- Sponsor's protocol ID
- L00070 IN 305 B0
- Other IDs
- 2008-004171-21, 2008
- Status last verified
- Apr 2022
- First submitted
- 24 Mar 2010
- Last updated
- 28 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Martin M, Campone M, Bondarenko I, Sakaeva D, Krishnamurthy S, Roman L, Lebedeva L, Vedovato JC, Aapro M. Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane. Ann Oncol. 2018 May 1;29(5):1195-1202. doi: 10.1093/annonc/mdy063.
PubMed 29447329
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Trial of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant.
- ClinicalTrials.gov ID
- NCT01095003
- Acronym / sponsor ID
- L00070 IN 305 B0
- Conditions
- Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 770 participants (actual)
- Lead sponsor
- Pierre Fabre MedicamentIndustry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 29 Mar 2010 (estimated)
- Results
- Posted 13 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The increasing use of anthracyclines and taxanes in the adjuvant, neoadjuvant and first-line metastatic settings, led to a raise of patients presenting with metastatic breast cancer after treatment with these agents. Options for the treatment of patients who have progressed after an anthracycline and a taxane are limited. The high level of in-vitro synergy of vinflunine combined with 5-fluorouracil (5-FU) together with the good tolerance and the encouraging response rate observed while combining IV vinflunine to oral capecitabine make it a promising combination to investigate further in a phase III trial. This phase III trial will evaluate the effectiveness and the safety profile of such combination for the treatment of patient with advanced breast cancer previously treated with or resistant to anthracycline and taxane resistant.
Detailed description
This multicentre, open-label, randomised, Phase III study will enrol 764 patients with advanced breast cancer who have previously been treated with or are resistant to an anthracycline and who are taxane resistant. Patients will be randomised in a 1:1 ratio to receive vinflunine plus capecitabine (Arm A) or capecitabine alone (Arm B).
Randomisation will be stratified according to a minimization procedure:
- Resistance to anthracyclines ("yes" versus "no"), Relapse ≤ 12 months in the adjuvant or neoadjuvant setting or progression ≤ 4 months in the metastatic setting,
- Karnofsky performance status ("90-100" versus "70-80"),
- Measurable disease ("yes" versus "no"),
- The number of prior lines of chemotherapy in the metastatic setting ("0" versus "1" versus "> 1") and,
- Study site.
Patients randomised in Arm A will receive:
- Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute i.v. infusion and,
- Capecitabine which will be self-administered by the patient in an outpatient setting. Patients will take 825 mg/m² twice daily per os for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest. A cycle of therapy is defined as 3 weeks.
For patients randomised in Arm B, capecitabine will be self administered by the patient in an outpatient setting. Patients will take 1250 mg/m² twice daily per os for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest. A cycle of therapy is defined as 3 weeks.
The doses and timing of treatment will be modified based on toxicities experienced by the patient.
Patients will be assessed for toxicity, tumour response and progression at regular intervals during treatment. Patients will be evaluated for safety if they received any study drug. Laboratory values, adverse events and other symptoms will be graded.
Tumour response, progression-free survival and duration of response will be evaluated for all randomised patients. Tumour assessment is to be performed every 6 weeks (+/- 3 working days) from randomisation (regardless of the timing of treatment cycles) until disease progression is documented. Patients who discontinue protocol treatment for reasons other than disease progression will have tumour assessments every 6 weeks until documented disease progression. Patients may continue to receive additional cycles of therapy until progressive disease or intolerable toxicity.
Quality of Life assessment, will be measured by EORTC QLQ-C30 and QLQ-BR23 questionnaires, which will be completed by patients.
The primary endpoint for the trial is progression free survival calculated from the date of randomization until the date of progression or the date of death whatever the reason of death. The analysis of Progression-Free Survival is planned to take place when 615 progressions or deaths have been observed. One interim safety analysis is planned and will take place when 50 patients of each arm have completed at least one cycle of study treatment. It is anticipated that up to 170 active study centres will participate, and that accrual will be completed in approximately 30 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vinflunine plus Capecitabine | Experimental | Drug: Vinflunine plus CapecitabinePatients received (in combination with capecitabine) • Vinflunine at the dose of 280 mg/m² and as a 20-minute IV. infusion on day 1 of each cycle repeated every 3 weeks. |
| Capecitabine single-agent | Active comparator | Drug: CapecitabineCapecitabine at the dose of 825mg/m² per os twice per day each morning and each evening for 14 consecutive days beginning on day 1 of each cycle repeated every 3 weeks (self-administered). |
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- female patients
- 21 years of age or older
- histologically/cytologically confirmed carcinoma of the breast
- documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy
- either one, two or three prior chemotherapy regimens
Key exclusion criteria (10 listed)
- known or clinical evidence of brain metastasis or leptomeningeal involvement
- pulmonary lymphangitis or symptomatic pleural effusion
- any serious, concurrent uncontrolled medical disorder
- history of second primary malignancy
- preexisting motor/sensory peripheral neuropathy
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 |
|---|---|---|
| Vinflunine plus CapecitabineAlso: JAVLOR, L00070 INVinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks | Drug | Vinflunine plus Capecitabine |
| CapecitabineAlso: XELODACapecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks | Drug | Capecitabine single-agent |
Primary outcome
Progression Free Survival
Time frame: Baseline up to 2 years 7 months
PFS is defined as time from date of randomization to date of the first documentation of objective tumor progression (according to the Independent Response Review Committee (IRC) and based on RECIST version 1.1) or death due to any cause. The PFS was primarily analysed in the Intent-to-treat (ITT) population. Patients lost to follow-up, or without a known record of progression or death at time of analysis had the progression-free survival censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression, whichever occurs last.
4 secondary outcomes
Overall Survival
Time frame: Baseline upto 3 years 10 months
Overall Response Rate (ORR)
Time frame: Baseline upto 2 years 7 months
Disease Control Rate
Time frame: Baseline up to 2 years 7 months
Duration of Response
Time frame: Baseline up to 2 years 7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29447329Martin M, Campone M, Bondarenko I, Sakaeva D, Krishnamurthy S, Roman L, Lebedeva L, Vedovato JC, Aapro M. Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane. Ann Oncol. 2018 May 1;29(5):1195-1202. doi: 10.1093/annonc/mdy063.
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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.
Jean-Claude VEDOVATO study director
Pierre Fabre Medicament
110 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vinflunine plus Capecitabine and Capecitabine in people with Breast Cancer, run by Pierre Fabre Medicament at 110 sites in 21 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 10 inclusion and 10 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 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 110 sites in France, Russia, India, Italy, United Kingdom and 16 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 13 Sep 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 (time frame: Baseline up to 2 years 7 months). 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 NCT01095003, which also lists 1 linked publication.
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 28 Apr 2022.