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

NCT ID: NCT01953003

Last Updated: 2019-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-07-31

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).

Detailed Description

RECIST 1.1 will be used for tumor assessment CTC - CAE version 3.0 will be used for safety assessment

Conditions

Malignant Neoplasm of Breast

Study Design

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

Study Groups

Arm A : iv vinflunine plus Capecitabine

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.

Group Type: EXPERIMENTAL

vinflunine

Intervention Type: DRUG

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

Capecitabine

Intervention Type: DRUG

Arm A : 1650 mg/m² Arm B : 2500 mg/m²

capecitabineArm B : capecitabine

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

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Arm A : 1650 mg/m² Arm B : 2500 mg/m²

Interventions

vinflunine

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

Intervention Type: DRUG

Capecitabine

Arm A : 1650 mg/m² Arm B : 2500 mg/m²

Intervention Type: DRUG

Other Intervention Names

Javlor; xeloda; from day 1 to day 14

Eligibility Criteria

Inclusion Criteria

1. Written informed consent

2. Histologically or cytologically confirmed Her-2 negative carcinoma of the breast

3. Documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy

4. 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.

5. 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

6. Documented progression on or within 12 months of the most recent chemotherapy.

7. Prior hormone therapy is allowed

8. Prior radiation therapy is allowed to less than 30% of the bone marrow

9. LMeasurable or non measurable disease defined according to RECIST V1.1

10. Adequate recovery from recent surgery

11. Estimated life expectancy superior or equal of 12 weeks

12. KPS equal or superior to 70%

13. Age equal or superior to 21 years and < 80 years

14. ANC) equal or superior to 1.5 x 109/L, platelet count equal or superior to 100 x109/L and haemoglobin > 10 g/dL.

15. 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.

16. Calculated creatinine clearance superior or equal to 50 mL/min

17. Normal ECG

18. Patients on coumadin or warfarin must be on stable doses and INR inferior or equal to 3

19. Women of childbearing potential must be using a medically accepted method of contraception. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first treatment administration.

20. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial.

Exclusion Criteria

1. Known or with clinical evidence of brain metastasis or leptomeningeal involvement.

2. Pulmonary lymphangitis or symptomatic pleural effusion (grade > 2) that results in pulmonary dysfunction requiring active treatment.

3. Patients having received any other experimental drug or chemotherapy within 30 days

4. 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

5. Pre-existing motor/sensory peripheral neuropathy of CTCAE version 3.0 grade >1

6. Patients having received > 3 regimens of chemotherapy

7. Prior therapy with capecitabine and/or vinca-alkaloids

8. History of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or any contra indication to any of the study drugs

9. Known or suspected DPD

10. Pregnant or lactating; With positive pregnancy test at inclusion

11. 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

12. Known history of HIV infection

13. Inability to take and/or absorb oral medication

14. 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.

15. Prior BMT or autologous stem cell infusion following high-dose chemotherapy.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Binghe XU, MD

Role: STUDY_CHAIR

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

Locations

Beijing, , China

Changchun, , China

Chengdu, , China

Dalian, , China

Fuzhou, , China

Hangzhou, , China

Harbin, , China

Jinan, , China

Nanjing, , China

Shanghai, , China

Shenyang, , China

Tianjin, , China

Wuhan, , China

NUH

Singapore, , Singapore

Gleneagles Hospital

Singapore, , Singapore

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Countries

China; Singapore; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

L00070 IN 311 B0

Identifier Type: -

Identifier Source: org_study_id