A phase II study evaluating the role of the combination of Vinorelbine,cyclophosphamide and capecitabine administered metronomically, that means low doses daily orally, in patients with advanced breast cancer

• Conditions: Metastatic breast cancer; MedDRA version: 14.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-024266-21-IT
• Lead Sponsor: ISTITUTO EUROPEO DI ONCOLOGIA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

- Pre- or post-menopausal women (age =18 years) with histologically or citologically (cell block) proven, locally advanced (inoperable) or metastatic breast carcinoma. Immunohistochemical evaluation of ER, PgR, HER2, and EGFR according to EIO (European Institute of oncology) guidelines is mandatory.
- Patients with ER>1% and/or PgR >1%
- Patients with HER-2/neu overexpressed tumors, are eligible if they had received previous trastuzumab therapy for advanced disease, and/or a treatment with anti HER2 targeted therapy.
- Patients fulfilling one of the following criteria:
- Patients with measurable disease as per RECIST 1.1 criteria. This is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as = 20 mm with conventional techniques or as = 10 mm with spiral CT scan
- Patients with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST 1.1 criteria. Bone lesions must be evaluable by plain CT or MRI. Patients with lesions identified only on radionucleotide bone scan are not eligible.
- Patients may have received any primary and/or adjuvant therapies, as any previous lines of chemotherapy and endocrine therapy for advanced disease. Patients may have received metronomic capecitabine, methotrexate and cyclophosphamide in adjuvant setting at least 12 months before study entry
- Previous treatment with capecitabine, cyclophosphamide and vinorelbine not in metronomic schedule for advanced disease is allowed, provided that the patient has progressive disease at study entry and the patients should not be defined as refractory” to treatments (PR or CR or SD > 6 months).
- Patients may have had previous hormonal therapy as treatment of metastatic disease provided that the patient has progressive disease at study entry. Hormonal therapy must be discontinued prior to study entry, excluding LH-RH analogue
- Life expectancy greater than 6 months.
- ECOG performance status =2
- Patients must have normal organ and marrow function
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Previous metronomic chemotherapy for advanced disease with capecitabine, cyclophosphamide and vinorelbine
- Triple negative subtypes (ER: 0% PgR:0% Her2: negative)
- Patients defined as refractory” to capecitabine, cyclophosphamide and vinorelbine (PD or SD < 6 months).
- Presence of sintomatic cerebral or leptomeningeal involvement.
- Previous or concomitant other malignancy except basal or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Malabsorption syndrome or disease affecting significantly gastrointestinal function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine
- Concurrent treatment with any other anti-cancer therapy except LHRH analogue.
- Patients with pre-existing motor or sensory peripheral neuropathy grade 2 according to NCI criteria

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess safety and efficacy of the combination;Secondary Objective: To assess the efficacy of VEX combination in terms of overall clinical benefit, defined as the objective response rate plus the rate of stable disease lasting longer than 24 weeks.;Primary end point(s): Time To Progression;Timepoint(s) of evaluation of this end point: at 3 and 5 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To assess the efficacy in terms of overall clinical benefit, defined as the objective response rate plus the rate of stable disease lasting longer than 24 weeks.;Timepoint(s) of evaluation of this end point: 36 months