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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Vinorelbine-Docetaxel
* Drug: Vinorelbine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maintenance treatment<br>Initial treatment Vinorelbine-Docetaxel Vinorelbine I.V: 20mg/m2 D1 Docetaxel: 60mg/m2 D1 Vinorelbine Oral: 60mg/m2 D8 Every 3 weeks for 6 cycles Followed by: Oral Vinorelbine 60mg/m2 D1, D8 or 80mg/m2 D1, D8 (dose schedule at investigator's discretion) Every 3 weeks until disease progression, unacceptable toxicities or patient refusal to continue | Drug: Vinorelbine-Docetaxel<br>* Vinorelbine I.V: 20mg/m2 D1 Docetaxel: 60mg/m2 D1 Vinorelbine Oral: 60mg/m2 D8 Every 3 weeks x 6 cycles<br>* Other names: Taxotere;Drug: Vinorelbine<br>* Oral Vinorelbine 60mg/m2 or 80mg/m2 D1, D8 every 3 weeks until disease progression, unacceptable toxicities or patient refusal to continue (dose schedule is at investigator's discretion)<br>* Other names: Navelbine Oral;|
| Experimental: Observation arm<br>Initial treatment: Vinorelbine-Docetaxel Vinorelbine I.V: 20mg/m2 D1 Docetaxel: 60mg/m2 D1 Vinorelbine Oral: 60mg/m2 D8 Every 3 weeks for 6 cycles Patients in the observation arm will not be administered any treatment after Vinorelbine-Docetaxel | Drug: Vinorelbine-Docetaxel<br>* Vinorelbine I.V: 20mg/m2 D1 Docetaxel: 60mg/m2 D1 Vinorelbine Oral: 60mg/m2 D8 Every 3 weeks x 6 cycles<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time To Disease Progression of patients who are treated with Vinorelbine-Docetaxel followed by maintenance oral Vinorelbine vs patients treated with Vinorelbine-Docetaxel without maintenance treatment |  | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate |  | Up to 36 months | 
| Duration of Response |  | Up to 36 months | 
| Quality of Life |  | Up to 36 months | 
| Number and percentage of participants with Adverse Events |  | Participants will be followed for the entired duration of the study, an expected average of 60 months | 
| 3-Y Overall Survival |  | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Vinorelbine, Oral Chemotherapy, Metastatic Breast Cancer, Advanced Breast Cancer, Maintenance treatment