Maintenance Oral Vinorelbine or Observation After Vinorelbine-Docetaxel First Line Chemotherapy in Advanced Breast Ca

TNM Trial: Upfront Docetaxel [T] and Alternating iv and Oral Vinorelbine [N] Followed, by Either Maintenance Oral Vinorelbine, or Observation for Advanced Breast Cancer

This 2 arms study will assess the efficacy and safety of the Vinorelbine-Docetaxel combination given as an initial upfront treatment (first line) to all metastatic breast cancer patients enrolled. Patients having a disease control following initial treatment, will be randomized to either oral Vinorelbine maintenance arm or Observation arm. The trial will also compare the efficacy and safety of maintenance oral Vinorelbine versus Observation.

To our knowledge, this is the first trial evaluating the role of oral Vinorelbine as a maintenance therapy versus observation following a first line treatment with iv/oral Vinorelbine+Docetaxel. Eligible patients will be enrolled in the trial to receive 6 cycles of iv(D1)/oral(D8) Vinorelbine + Docetaxel. For responding and SD patients, after the 6 cycles, they will be randomized either in observation arm or to receive a maintenance chemotherapy with oral Vinorelbine. The oral form of the drug was found to be most appropriate for a long term treatment allowing to preserve QoL of the patients. Oral Vinorelbine will be administered on D1, D8 every 3 weeks during maintenance treatment, until PD, unacceptable toxicity or patient refusal to continue. The trial will assess efficacy/safety of initial Vinorelbine-Docetaxel combination as well as the benefits of maintenance chemotherapy with oral Vinorelbine.

Inclusion Criteria:

• Written informed consent
• Patients >=18 years of age
• Histologically or cytologically confirmed adenocarcinoma of the breast that is now metastatic or locally-recurrent and inoperable with curative intent
• Measurable and/or non-measurable disease
• The patient's primary and/or metastatic tumor is HER2 neu negative
• Documented metastatic disease previously untreated with palliative chemotherapy
• Adjuvant or neo-adjuvant chemotherapy (including treatment with docetaxel or any other chemotherapy) is allowed with a disease free survival of at least 6 months
• No symptom or sign of brain metastasis

Exclusion Criteria:

• Operable local recurrence
• Ascites or pericardial effusion as only site of metastasis
• Symptomatic peripheral neuropathy > grade 1 according to the NCI Common Toxicity Criteria
• Radiotherapy to all areas of evaluable disease within the previous 4 weeks
• Disease significantly affecting absorption
• Severe hepatic insufficiency
• Patient previously treated with chemotherapy for their metastatic disease