Phase II Study of Metronomic Treatment With Daily Oral Vinorelbine as First-line Chemotherapy in Patients With Advanced/Metastatic HR+/HER2- Breast Cancer Resistant to Endocrine Therapy
Overview
- Phase
- Phase 2
- Intervention
- Vinorelbine
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Johannes Gutenberg University Mainz
- Enrollment
- 9
- Locations
- 8
- Primary Endpoint
- Clinical Benefit Rate (CBR)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of the trial is to investigate the efficacy of metronomic treatment with daily oral vinorelbine in terms of clinical benefit rate based on local radiological assessment in patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy.
Detailed Description
In terms of the chronic nature of advanced/metastatic breast cancer, there is a high medical need for new treatment options after failure of hormonal treatment that prolong the interval to the start of intensive cytotoxic therapy, which is commonly associated with impaired quality of life (QoL) and potentially serious side effects. In this respect, metronomic treatment with daily administration of oral vinorelbine could provide an efficacious treatment option with limited toxicities. Accordingly, this national, multi-centre, open-label, single-arm phase II trial aims to investigate a truly metronomic schedule with daily oral vinorelbine in HR+/HER2-patients with metastatic breast cancer resistant to endocrine therapy, by assessing efficacy and safety. Oral vinorelbine will be administered at a daily dose of 30 mg (flat dose without any adaptation to body weight or body surface area) without breaks. Treatment will continue until disease progression, occurrence of unacceptable toxicity, patient's refusal or investigator's decision to stop the treatment. In the course of the study, the following interim and final analyses will be done: i) 1st interim analysis (safety): This analysis will be performed on the basis of 10 patients, who were initially included into the study and who are eligible for safety evaluation; frequency statistics of (serious) adverse events will be analysed. ii) 2nd interim analysis (efficacy): This analysis will be performed at the completion of the 1st Simon stage. iii) Final analysis (complete): This analysis will be performed after completion of the follow-up phase (6 months of follow-up after Last Patient Last Treatment).
Investigators
Marcus Schmidt, MD
Univ.-Prof. Dr. med.
Johannes Gutenberg University Mainz
Eligibility Criteria
Inclusion Criteria
- •Written (personally dated and signed) informed consent prior to the performance of any trial specific procedure
- •Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and/or the follow-up schedule
- •Female patient ≥ 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1, which the investigator assesses as being stable at time of screening
- •Estimated life expectancy ≥ 16 weeks
- •Histologically confirmed adenocarcinoma of the breast
- •Documented locally advanced or metastatic disease, previously untreated by palliative chemotherapy and not amenable to any curative treatment
- •Hormone receptor positive disease determined by ≥ 1% positive stained cells for oestrogen and/or progesterone receptor by immunohistochemistry on the primary tumour or on a metastatic site
- •HER2-negative disease assessed by 0-1+ immuno-histochemistry (IHC) or 2+ IHC with negative fluorescence in situ hybridization (FISH) or CISH) on the primary tumour or on a metastatic site
- •Availability of archival (from the most recently obtained sample) or fresh tumour tissue from patients included in the trial for the analysis of relevant metronomic biomarkers; one tumour block (preferred) or a minimum of 12 (recommended: 15) unstained slides to be provided
Exclusion Criteria
- •No recovery to ≤ Grade (G)1 side effects (exception: alopecia) of any prior anti-neoplastic treatment
- •Aggressive locally advanced or metastatic breast cancer disease requiring systemic combination therapy
- •Known or suspected central nervous system (CNS) and/or leptomeningeal involvement
- •Current peripheral neuropathy ≥ G2
- •Dysphagia or inability to swallow oral medication
- •Malabsorption syndrome or disease significantly affecting GI-function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine
- •Other serious illness or medical condition, such as but not limited to:
- •Clinically significant cardiac disease or impaired cardiac function (such as: congestive heart failure requiring treatment (NYHA ≥ II); eft ventricular ejection fraction (LVEF) \< 50%; significant cardiac arrhythmia; atrial fibrillation; conduction abnormality such as congenital long QT syndrome or high grade/complete atrioventricular (AV)-blockage; acute coronary syndrome including myocardial infarction, unstable angina pectoris, coronary artery bypass graft, coronary angioplasty or stenting, if \< 3 months prior to registration; QTcF \> 480 msec at screening)
- •Uncontrolled hypertension (\> 140/100 mmHg at rest (average of 3 consecutive readings))
- •Unstable diabetes mellitus
Arms & Interventions
Vinorelbine Oral
Test product: Navelbine® 20 mg / 30 mg soft capsules
Intervention: Vinorelbine
Outcomes
Primary Outcomes
Clinical Benefit Rate (CBR)
Time Frame: 24 weeks after start of treatment.
The primary endpoint is the determination of the Clinical Benefit Rate (CBR) at 24 weeks after start of treatment. The response to treatment is measured by computer tomography (CT) or magnetic resonance imaging (MRI) for measurable lesions and evaluation for non-measurable lesions at 24 weeks after start of treatment.
Secondary Outcomes
- Time to treatment failure (TTF)(6 months after last patient last treatment)
- Overall response rate (ORR)(6 months after last patient last treatment)
- Disease control rate (DCR)(6 months after last patient last treatment)
- Duration of response (DoR)(6 months after last patient last treatment)
- Number of patients with treatment-related adverse events as assessed by CTCAE v4.0(6 months after last patient last treatment)
- Patient's symptoms and health-related quality of life(6 months after last patient last treatment)
- Duration of stable disease (DoSD)(6 months after last patient last treatment)
- Histopathological parameters(before start of treatment and upon progression, assessed up to 6 months after last patient last treatment)
- Duration of disease control (DoDC)(6 months after last patient last treatment)
- Overall survival (OS)(6 months after last patient last treatment)
- Biomarker profiles(before start of treatment, during treatment period and upon progression, assessed up to 6 months after last patient last treatment)
- Progression-free survival (PFS)(6 months after last patient last treatment)