Clinical trial NCT01095003: Trial of Vinflunine Plus Capecitabine in Advanced Breast Cancer
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
First posted: 2010-03-29
Enrollment: 770
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival
timeFrame: Baseline up to 2 years 7 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Baseline upto 3 years 10 months
measure: Overall Response Rate (ORR)
timeFrame: Baseline upto 2 years 7 months
measure: Disease Control Rate
timeFrame: Baseline up to 2 years 7 months
measure: Duration of Response
timeFrame: Baseline up to 2 years 7 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Quilmes
country: Argentina
city: Rosario
country: Argentina
city: San Martin
country: Argentina
city: Tucuman
country: Argentina
city: Gomel
country: Belarus
city: Grodno
country: Belarus
city: Minsk
country: Belarus
city: Vitebsk
country: Belarus
city: Bruxelles
country: Belgium
city: Liège
country: Belgium
city: Curitiba
country: Brazil
city: Porto Alegre
country: Brazil
city: Santo Andre
country: Brazil
city: Sao Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Brno
country: Czechia
city: Jihlava
country: Czechia
city: Tallinn
country: Estonia
city: Angers
country: France
city: Caen
country: France
city: Dijon
country: France
city: Le Mans
country: France
city: Lorient
country: France
city: Lyon
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Saint-Brieuc
country: France
city: Saint-Cloud
country: France
city: Saint-Herblain
country: France
city: Tours
country: France
city: Villejuif
country: France
city: Budapest
country: Hungary
city: Szekesfehervar
country: Hungary
city: Szolnok
country: Hungary
city: Aurangabad
country: India
city: Bangalore
country: India
city: Bhopal
country: India
city: Calcutta
country: India
city: Calicut
country: India
city: Jaipur
country: India
city: Mumbai
country: India
city: Patna
country: India
city: Pune
country: India
city: Trivandrum
country: India
city: Avellino
country: Italy
city: Cagliari
country: Italy
city: Cremona
country: Italy
city: Fabriano
country: Italy
city: Milano
country: Italy
city: Monza
country: Italy
city: Padova
country: Italy
city: Pisa
country: Italy
city: Rozzano
country: Italy
city: Verona
country: Italy
city: Chihuahua
country: Mexico
city: Leon
country: Mexico
city: Mexico City
country: Mexico
city: Saltillo
country: Mexico
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lubin
country: Poland
city: Warsawa
country: Poland
city: Arkhangelsk
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saratov
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Tambov
country: Russian Federation
city: Ufa
country: Russian Federation
city: Vladimir
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Nis
country: Serbia
city: Sremska Kamenica
country: Serbia
city: Durban
country: South Africa
city: Kimberley
country: South Africa
city: Pretoria
country: South Africa
city: Sandton
country: South Africa
city: Barcelona
country: Spain
city: Lleida
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Valencia
country: Spain
city: Genolier
country: Switzerland
city: Lausanne
country: Switzerland
city: Winterthur
country: Switzerland
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Cherkasy
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Khmelnytskyï
country: Ukraine
city: Kyiv
country: Ukraine
city: Simferopol
country: Ukraine
city: Belfast
country: United Kingdom
city: Chelmsford
country: United Kingdom
city: Keighley
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Peterborough
country: United Kingdom
city: Portsmouth
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southend-on-Sea
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Pierre Fabre Medicament
name: Jean-Claude VEDOVATO
role: STUDY_DIRECTOR
References:
citation: 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.