Trial of Vinflunine Plus Capecitabine in Advanced Breast Cancer

April 6, 2022 updated by: Pierre Fabre Medicament

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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:

  1. Resistance to anthracyclines ("yes" versus "no"), Relapse ≤ 12 months in the adjuvant or neoadjuvant setting or progression ≤ 4 months in the metastatic setting,
  2. Karnofsky performance status ("90-100" versus "70-80"),
  3. Measurable disease ("yes" versus "no"),
  4. The number of prior lines of chemotherapy in the metastatic setting ("0" versus "1" versus "> 1") and,
  5. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
770

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
      • Quilmes, Argentina
      • Rosario, Argentina
      • San Martin, Argentina
      • Tucuman, Argentina
  • Belarus
      • Gomel, Belarus
      • Grodno, Belarus
      • Minsk, Belarus
      • Vitebsk, Belarus
  • Belgium
      • Bruxelles, Belgium
      • Liège, Belgium
  • Brazil
      • Curitiba, Brazil
      • Porto Alegre, Brazil
      • Santo Andre, Brazil
      • Sao Paulo, Brazil
  • Bulgaria
      • Plovdiv, Bulgaria
      • Sofia, Bulgaria
      • Stara Zagora, Bulgaria
  • Czechia
      • Brno, Czechia
      • Jihlava, Czechia
  • Estonia
      • Tallinn, Estonia
  • France
      • Angers, France
      • Caen, France
      • Dijon, France
      • Le Mans, France
      • Lorient, France
      • Lyon, France
      • Montpellier, France
      • Nantes, France
      • Saint-Brieuc, France
      • Saint-Cloud, France
      • Saint-Herblain, France
      • Tours, France
      • Villejuif, France
  • Hungary
      • Budapest, Hungary
      • Szekesfehervar, Hungary
      • Szolnok, Hungary
  • India
      • Aurangabad, India
      • Bangalore, India
      • Bhopal, India
      • Calcutta, India
      • Calicut, India
      • Jaipur, India
      • Mumbai, India
      • Patna, India
      • Pune, India
      • Trivandrum, India
  • Italy
      • Avellino, Italy
      • Cagliari, Italy
      • Cremona, Italy
      • Fabriano, Italy
      • Milano, Italy
      • Monza, Italy
      • Padova, Italy
      • Pisa, Italy
      • Rozzano, Italy
      • Verona, Italy
  • Mexico
      • Chihuahua, Mexico
      • Leon, Mexico
      • Mexico City, Mexico
      • Saltillo, Mexico
  • Poland
      • Bialystok, Poland
      • Gdansk, Poland
      • Krakow, Poland
      • Lodz, Poland
      • Lubin, Poland
      • Warsawa, Poland
  • Russian Federation
      • Arkhangelsk, Russian Federation
      • Chelyabinsk, Russian Federation
      • Moscow, Russian Federation
      • Ryazan, Russian Federation
      • Saratov, Russian Federation
      • St-Petersburg, Russian Federation
      • Stavropol, Russian Federation
      • Tambov, Russian Federation
      • Ufa, Russian Federation
      • Vladimir, Russian Federation
      • Volgograd, Russian Federation
  • Serbia
      • Nis, Serbia
      • Sremska Kamenica, Serbia
  • South Africa
      • Durban, South Africa
      • Kimberley, South Africa
      • Pretoria, South Africa
      • Sandton, South Africa
  • Spain
      • Barcelona, Spain
      • Lleida, Spain
      • Madrid, Spain
      • Oviedo, Spain
      • Valencia, Spain
  • Switzerland
      • Genolier, Switzerland
      • Lausanne, Switzerland
      • Winterthur, Switzerland
  • Taiwan
      • Taipei, Taiwan
      • Taoyuan, Taiwan
  • Ukraine
      • Cherkasy, Ukraine
      • Dnipropetrovsk, Ukraine
      • Donetsk, Ukraine
      • Khmelnytskyï, Ukraine
      • Kyiv, Ukraine
      • Simferopol, Ukraine
  • United Kingdom
      • Belfast, United Kingdom
      • Chelmsford, United Kingdom
      • Keighley, United Kingdom
      • London, United Kingdom
      • Nottingham, United Kingdom
      • Peterborough, United Kingdom
      • Portsmouth, United Kingdom
      • Sheffield, United Kingdom
      • Southend-on-Sea, United Kingdom
      • Sutton, United Kingdom

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vinflunine plus Capecitabine

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.
Drug: Vinflunine plus Capecitabine

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

Other Names:
  • JAVLOR
  • L00070 IN
Active Comparator: Capecitabine single-agent
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).
Drug: Capecitabine
Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Other Names:
  • XELODA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline up to 2 years 7 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Baseline upto 3 years 10 months
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.
Baseline upto 3 years 10 months
Overall Response Rate (ORR)
Time Frame: Baseline upto 2 years 7 months
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.
Baseline upto 2 years 7 months
Disease Control Rate
Time Frame: Baseline up to 2 years 7 months
Disease control rate defined (DCR) as the sum of confirmed complete response, confirmed partial response and stabilisation rate.
Baseline up to 2 years 7 months
Duration of Response
Time Frame: Baseline up to 2 years 7 months
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.
Baseline up to 2 years 7 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pierre Fabre Medicament

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jean-Claude VEDOVATO, Pierre Fabre Medicament

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 29, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 28, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • L00070 IN 305 B0
  • 2008-004171-21 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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