Phase III Study of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer

NCT01953003 | Completed Phase 3 Results

• 1 other identifier: L00070 IN 311 B0
• Study Type: interventional
• Target: 112
• Locations: 3 countries
• Sites: 18

Brief Summary

Options for the treatment of patients who have progressed after an anthracycline and a taxane are limited. Capecitabine currently has a role in this setting, yet as many as 80% of patients do not respond to this treatment and those who respond eventually develop clinical resistance. The antitumour activity of vinflunine has been demonstrated in patients with breast cancer after exposure to anthracycline and to taxane. Vinflunine plus capecitabine has been shown to be a feasible combination for patients previously treated with an anthracycline and a taxane. Each drug in combination can be administered at efficacious doses. This population has few therapeutic options with established clinical benefit. The development of a new regimen and potential new standard of care for this group is important.

• Primary objective:
• to compare in patients with advanced breast cancer pretreated with anthracycline and taxane the efficacy of the combination of vinflunine and capecitabine with capecitabine alone, in terms of progression-free survival.
• Secondary objectives:
• to evaluate the response rate, the time to response and the duration of response in both arms
• to compare the disease control rate between arms
• to evaluate the duration of disease control in both arms
• to evaluate the overall survival in both arms
• to evaluate safety Methodology This multicentre, open-label, randomised, Phase III study will enrol a total of 334 patients with advanced breast cancer who have previously been treated with an anthracycline and a taxane. Patients will be randomised in a 1:1 ratio to receive VFL plus capecitabine (Arm A) or capecitabine alone (Arm B).

Conditions

Malignant Neoplasm of Breast

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  The primary endpoint for the trial is progression-free survival calculated from the date of randomisation until the date of progression or the date of death whatever the cause of death. Patient who does not progressed will be censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression.

  progression date will be assessed evey 6 weeks starting from the randomization date until first documented progression or date of death from any cause whichever came first assessed up to 3 years

Study Arms (2)

Arm A : iv vinflunine plus Capecitabine

EXPERIMENTAL

Vinflunine dose 280 mg/m² on day 1 of each cycle every 3 weeks, Capecitabine 825 mg/m² twice daily orally for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest.

Drug: vinflunine; Drug: Capecitabine

capecitabineArm B : capecitabine

ACTIVE COMPARATOR

1250 mg/m² twice daily orally for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest

Drug: Capecitabine

Interventions

vinflunine DRUG

intravenous administration day 1 once every 3 weeks, 280 mg/m²

Also known as: Javlor

Arm A : iv vinflunine plus Capecitabine

Capecitabine DRUG

Arm A : 1650 mg/m² Arm B : 2500 mg/m²

Also known as: xeloda, from day 1 to day 14

Arm A : iv vinflunine plus Capecitabine; capecitabineArm B : capecitabine

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Histologically or cytologically confirmed Her-2 negative carcinoma of the breast
• Documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy
• One, two or three prior chemotherapy regimens including those administered in the neoadjuvant or adjuvant setting. At least one of the regimens must have been given for the treatment of advanced disease.
• Prior treatment must have included both an anthracycline and a taxane. minimum cumulative dose of 180 mg/m² of doxorubicin or of 300 mg/m² of epirubicin
• Documented progression on or within 12 months of the most recent chemotherapy.
• Prior hormone therapy is allowed
• Prior radiation therapy is allowed to less than 30% of the bone marrow
• LMeasurable or non measurable disease defined according to RECIST V1.1
• Adequate recovery from recent surgery
• Estimated life expectancy superior or equal of 12 weeks
• KPS equal or superior to 70%
• Age equal or superior to 21 years and \< 80 years
• ANC) equal or superior to 1.5 x 109/L, platelet count equal or superior to 100 x109/L and haemoglobin \> 10 g/dL.
• Bilirubin inferior or equal to 1.5 x upper limit of normal (ULN), AST and ALT inferior or equal to 2.5 x ULN or inferior or equal to 5 x ULN in the case of liver metastases, alkaline phosphatase inferior or equal to 5 x ULN.

You may not qualify if:

• Known or with clinical evidence of brain metastasis or leptomeningeal involvement.
• Pulmonary lymphangitis or symptomatic pleural effusion (grade \> 2) that results in pulmonary dysfunction requiring active treatment.
• Patients having received any other experimental drug or chemotherapy within 30 days
• History of second primary malignancy, except: bilateral breast carcinoma, in situ carcinoma of the cervix, adequately treated non melanomatous carcinoma of the skin, and other malignancy treated at least 5 years previously with no evidence of recurrence
• Pre-existing motor/sensory peripheral neuropathy of CTCAE version 3.0 grade \>1
• Patients having received \> 3 regimens of chemotherapy
• Prior therapy with capecitabine and/or vinca-alkaloids
• History of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or any contra indication to any of the study drugs
• Known or suspected DPD
• Female of childbearing potential who is unwilling or unable to use a medically accepted method to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and at least 3 months following the last dose of study treatment
• Known history of HIV infection
• Inability to take and/or absorb oral medication
• Any serious, concurrent uncontrolled medical disorder especially uncontrolled hypercalcaemia, congestive heart failure, uncontrolled high-risk hypertension, arrhythmia, angina pectoris or previous history of myocardial infarction within 6 months prior to randomisation.
• Prior BMT or autologous stem cell infusion following high-dose chemotherapy.

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (18)

Unknown Facility

Beijing, China

Location

Unknown Facility

Changchun, China

Location

Unknown Facility

Chengdu, China

Location

Unknown Facility

Dalian, China

Location

Unknown Facility

Fuzhou, China

Location

Unknown Facility

Hangzhou, China

Location

Unknown Facility

Harbin, China

Location

Unknown Facility

Jinan, China

Location

Unknown Facility

Nanjing, China

Location

Unknown Facility

Shanghai, China

Location

Unknown Facility

Shenyang, China

Location

Unknown Facility

Tianjin, China

Location

Unknown Facility

Wuhan, China

Location

NUH

Singapore, 119228, Singapore

Location

Gleneagles Hospital

Singapore, 258500, Singapore

Location

Unknown Facility

Kaohsiung City, Taiwan

Location

Unknown Facility

Taichung, Taiwan

Location

Unknown Facility

Taipei, Taiwan

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

vinflunine; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Early termination of the study. Efficacy analyses were reduced to a descriptive summary of the primary efficacy variable (PFS) in the ITT population. This did not demonstrate any additional benefit of supplementing CAPE with VFL. Abbreviated CSR.

Results Point of Contact

• Title: Karim Keddad, Head of Medical Unit
• Organization: Institut de Recherche Pierre Fabre, Toulouse France

Karim.keddad@pierre-fabre.com

+33.5.34.50.61.69

Study Officials

• Binghe XU, MD

  Cancer Institute & Hospital. Chinese Academy of Medical Sciences, Beijing

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: September 30, 2013
• Study Start: September 1, 2013
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: May 2, 2019
• Results First Posted: May 2, 2019

Record last verified: 2019-01

Locations

SG (2); TW (3); CN (13)