Trial of Vinflunine Plus Capecitabine in Advanced Breast Cancer

NCT ID: NCT01095003

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 770 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2015-10-31

Brief 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. 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:

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vinflunine plus Capecitabine

Intervention Type: DRUG

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

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).

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks

Interventions

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

Intervention Type: DRUG

Capecitabine

Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks

Intervention Type: DRUG

Other Intervention Names

JAVLOR; L00070 IN; XELODA

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Claude VEDOVATO

Role: STUDY_DIRECTOR

Pierre Fabre Medicament

Locations

Buenos Aires, , Argentina

Quilmes, , Argentina

Rosario, , Argentina

San Martín, , Argentina

San Miguel de Tucumán, , Argentina

Grodno, , Belarus

Homyel, , Belarus

Minsk, , Belarus

Vitebsk, , Belarus

Brussels, , Belgium

Liège, , Belgium

Curitiba, , Brazil

Porto Alegre, , Brazil

Santo André, , Brazil

São Paulo, , Brazil

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Stara Zagora, , Bulgaria

Brno, , Czechia

Jihlava, , Czechia

Tallinn, , Estonia

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

Budapest, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Aurangabad, , India

Bangalore, , India

Bhopal, , India

Calicut, , India

Jaipur, , India

Kolkata, , India

Mumbai, , India

Patna, , India

Pune, , India

Trivandrum, , India

Avellino, , Italy

Cagliari, , Italy

Cremona, , Italy

Fabriano, , Italy

Milan, , Italy

Monza, , Italy

Padua, , Italy

Pisa, , Italy

Rozzano, , Italy

Verona, , Italy

Chihuahua City, , Mexico

León, , Mexico

Mexico City, , Mexico

Saltillo, , Mexico

Bialystok, , Poland

Gdansk, , Poland

Krakow, , Poland

Lodz, , Poland

Lubin, , Poland

Warsaw, , Poland

Arkhangelsk, , Russia

Chelyabinsk, , Russia

Moscow, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Stavropol, , Russia

Tambov, , Russia

Ufa, , Russia

Vladimir, , Russia

Volgograd, , Russia

Kamenitz, , Serbia

Niš, , Serbia

Durban, , South Africa

Kimberley, , South Africa

Pretoria, , South Africa

Sandton, , South Africa

Barcelona, , Spain

Lleida, , Spain

Madrid, , Spain

Oviedo, , Spain

Valencia, , Spain

Genolier, , Switzerland

Lausanne, , Switzerland

Winterthur, , Switzerland

Taipei, , Taiwan

Taoyuan District, , Taiwan

Cherkasy, , Ukraine

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Khmelnytskyi, , Ukraine

Kyiv, , Ukraine

Simferopol, , Ukraine

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

Countries

Argentina; Belarus; Belgium; Brazil; Bulgaria; Czechia; Estonia; France; Hungary; India; Italy; Mexico; Poland; Russia; Serbia; South Africa; Spain; Switzerland; Taiwan; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29447329 (View on PubMed)

Other Identifiers

2008-004171-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

L00070 IN 305 B0

Identifier Type: -

Identifier Source: org_study_id