A Study of Vinflunine Plus Gemcitabine Versus Paclitaxel Plus Gemcitabine in Patients With Advanced Breast Cancer

NCT ID: NCT02054338

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1004 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2015-02-28

Brief Summary

The combination of vinflunine and gemcitabine in advanced breast cancer in comparison to paclitaxel and gemcitabine is based on the following points: the significant antitumour activity of vinflunine in metastatic breast cancer (MBC) as single agent after anthracycline-taxane exposure and recent phase I study results of the vinflunine plus gemcitabine is at least additive and both drugs have a distinct mechanism of action; since taxanes have been approved in the adjuvant setting and are widely used in the treatment of early breast cancer it is worthwhile to assess new combination chemotherapy regimens as first line therapy for metastatic breast cancer.

Detailed Description

This is a randomised, multicentre, open-label phase III study comparing antitumour efficacy of vinflunine plus gemcitabine versus paclitaxel plus gemcitabine, as first line treatment for patients with unresectable, locally recurrent or metastatic breast cancer after prior anthracycline-based adjuvant chemotherapy.

Patients with metastatic breast cancer are incurable using conventional therapy with antitumoural hormonal drugs or cytostatic agents. The median survival from diagnosis of metastatic disease to death is reported to be approximately 3 years. While newer chemotherapeutic agents have been able to achieve tumour shrinkage, no significant increases in overall survival have been demonstrated so far. One reason for this result may be that breast cancer has a longer disease time span than NSCLC, allowing for administration of multiple therapies with different modalities. These therapies confound overall survival regardless of whether the treatment is a first-line or a subsequent treatment. The combination of gemcitabine plus paclitaxel has demonstrated improvement in overall survival over paclitaxel alone as first line therapy in patients with locally recurrent or metastatic breast cancer, however, this study compared single agent versus combination chemotherapy.

Using overall survival as a primary endpoint in a trial Using overall survival as a primary endpoint in a trial comparing 2 different cytostatic combinations in the treatment of metastatic breast cancer requires a large phase III study to detect a clinically significant difference. The advantages with such an endpoint are that it is technically easy to monitor and it is not dependent on monitoring tumour status. However, since patients with breast cancer typically receive 3 or more lines of chemotherapy, it becomes difficult to assess the impact of a first-line therapy on overall survival (as proposed herein) due to the potential for confounding effects from later treatments. A more specific instrument -if closely monitored- is progression-free survival. This endpoint reflects the impact of a specific treatment modality on the disease at a given time period and is probably confounded neither by prior treatments nor by subsequent therapies. Progression-free survival also represents an important clinical achievement for patients with metastatic breast cancer.

Conditions

Advanced Breast Cancer

Study Design

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

Study Groups

vinflunine plus gemcitabine

vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks

Group Type: EXPERIMENTAL

Vinflunine+Gemcitabine

Intervention Type: DRUG

Vinflunine 320 mg/m² IV on day 1 and.Gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks

paclitaxel plus gemcitabine

paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks

Group Type: ACTIVE_COMPARATOR

Paclitaxel+Gemcitabine

Intervention Type: DRUG

paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1

Interventions

Vinflunine+Gemcitabine

Vinflunine 320 mg/m² IV on day 1 and.Gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks

Intervention Type: DRUG

Paclitaxel+Gemcitabine

paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1

Intervention Type: DRUG

Other Intervention Names

L0070 IN

Eligibility Criteria

Inclusion Criteria

• female patients
• 18 years or older but less than 75 years old
• histologically/cytologically confirmed breast cancer
• documented locally recurrent or metastatic breast cancer
• HER-2 negative or unknown
• prior neo- and/or adjuvant anthracycline-based chemotherapy
• measurable or non-measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0
• adequate haematological, hepatic and renal functions
• ECG without any clinically relevant abnormality

Exclusion Criteria

• known or clinical evidence of brain metastases or leptomeningeal involvement
• history of second primary malignancy
• patients having as sole tumour lesion: malignant effusion, lymphangitis, cystic lesion, bone lesion, and any other lesion not assessed by imaging techniques or colour photography
• pre-existing motor/sensory grade > 1 peripheral neuropathy
• prior therapy with vinca alkaloids and/or gemcitabine
• history of severe hypersensitivity to vinca alkaloids and/or gemcitabine or contraindication to any of these drugs
• pregnancy or breast feeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karim Keddad, MD, PhD

Role: STUDY_DIRECTOR

Employed Pierre Fabre Medicament

Other Identifiers

2006-001139-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

L00070 IN 303 B0

Identifier Type: -

Identifier Source: org_study_id