HR+/HER2- advanced/metastatic breast cancer
Conditions
Interventions
Trade Name: Navelbine
Product Name: Navelbine 20 mg/30 mg/80 mg
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: VINORELBINE Tartrate
CAS Number: 125317-39-7
Concentration unit: mg milligram(s)
Sponsors
Universitätsmedizin Mainz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written (personally dated and signed) informed consent prior to the per¬for¬man¬ce of any trial specific procedure 2. Absence of any psychological, familial, sociological or geographical con¬dition potentially hampering compliance with the study protocol and/or the follow-up schedule 3. Female patient = 18 years of age 4. ECOG performance status 0-1, which the investigator assesses as being stable at time of screening 5. Estimated life expectancy = 16 weeks 6. Histologically confirmed adenocarcinoma of the breast 7. Documented locally advanced or metastatic disease, previously untreated by palliative chemotherapy and not amenable to any curative treatment 8. 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 9. HER2-negative disease (assessed by 0-1+ IHC or 2+ IHC with negative FISH or CISH) on the primary tumour or on a metastatic site 10. Availability of archival (from the most recently obtained sample) or fresh tumour tissue from patients included in the trial for the analysis of relevant me¬tro¬¬nomic biomarkers; one tumour block (preferred) or a minimum of 12 (recommended: 15) unstained slides to be provided 11. Relapse = 12 months from end of adjuvant hormonal therapy or pro¬gres¬sion during/after = 1 line of endocrine therapy in the metastatic set¬ting and/or no longer candidate for further endocrine therapy 12. Prior (neo-)adjuvant chemotherapy is allowed, if the interval between end of chemotherapy and date of registration is > 12 months 13. Prior treatment with everolimus and/or palbociclib in the frame of hormonal therapy is allow¬ed 14. Complete staging before registration (CT/MRI thorax and CT/MRI abdo¬men/pelvis = 28 days before registration; bone scan = 3 months before registra¬tion) 15. Presence of = 1 measurable lesion as per RECIST 1.1, which has not been previously irradiated 16. Adequate bone marrow, hepatic and renal function as defined by the following laboratory values: • Absolute neutrophil count (ANC) = 1,500/mm3 • Platelet count = 100,000/mm3 • Haemoglobin = 10 g/dL • Total serum bilirubin = 1.5 x ULN (= 3 x ULN in case of liver metasta¬s¬es) • Liver transaminases = 2.5 x ULN (= 5 x ULN in case of liver metasta¬s¬es) • Alkaline phosphatase = 5 x ULN • Creatinine = 1.5 x ULN (creatinine clearance should be assessed based on the Cock¬roft-Gault-formula in case of borderline values and should then be = 50 ml/min) 17. Women of childbearing potential must be using a medically accepted method of contraception to avoid pregnancy during 2 months preceding registration, throughout the study period and up to 3 months after last dose of study treatment in such a manner that the risk of pregnancy is mini¬mised; reliable contraception comprises sexual abstinence, male sterilization or double barrier methods (e.g. a combination of male condom with diaphragm). 18. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment 19. Ability of the patient to understand the character and the individual consequences of this clinical trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. No recovery to = Grade (G)1 side effects (exception: alopecia) of any prior anti-neoplastic treatment 2. Aggressive locally advanced or metastatic breast cancer disease requiring systemic combination therapy 3. Known or suspected CNS and/or leptomeningeal involvement 4. Current peripheral neuropathy = G2 5. Dysphagia or inability to swallow oral medication 6. 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 7. 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); LVEF 480 msec at screening) • Uncontrolled hypertension (>140/100 mmHg at rest (average of 3 consecutive readings)) • Unstable diabetes mellitus • Uncontrolled hypercalcemia • Clinically significant active infections (current or within the last 2 weeks prior to registration) • Previous organ allograft 8. Prior treatment with vinorelbine or other vinca alkaloids 9. Concomitant endocrine therapy (e.g. tamoxifen, aromatase inhibitors, fulvestrant) for advanced breast cancer 10. Concomitant use of yellow-fever vaccination or other attenuated life vaccine 11. Concomitant treatment with strong CYP3A4-inhibitors or strong CYP3A4-inducers (discontinuation before registration is acceptable, if medically feasible and ethically acceptable) 12. Necessity to undergo long-term oxygen therapy 13. Major surgery = 28 days prior to registration and/or no recovery from side effects of such therapy to baseline condition or = G1 14. Radiotherapy = 28 days prior to registration, no recovery from side effects of such therapy to baseline condition or = G1 and/or irradiation of =30% of bone marrow 15. Known hypersensitivity to vinca alkaloids, soy, peanut or any of the excipients contained in the oral vinorelbine capsules 16. Participation in another clinical trial with any investigational drug = 30 days prior to registration 17. History of another malignancy within the past 5 years prior to registration, except cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix 18. Pregnant or nursing (lactating) woman
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the efficacy of metronomic treatment with daily oral vinorelbine in terms of clinical benefit rate (CBR) based on local radiological assessment using RECIST 1.1 in patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy;Secondary Objective: - To further assess the efficacy of metronomic treatment with daily oral vinorelbine in terms of overall response rate (ORR), disease control rate (DCR), duration of disease control (DoDC), duration of stable disease (DoSD), duration of response (DoR), pro- gression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS) – To assess the safety and tolerability of metronomic treatment with daily oral vinorelbine – To assess the effect of metronomic treatment with daily oral vinorelbine on patient’s symptoms and health-related quality of life (HRQoL);Primary end point(s): Determination of the CBR (SD+PR+CR) at 24 weeks after start of treatment;Timepoint(s) of evaluation of this end point: 24 weeks after start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): – Estimation of ORR, DCR (overall and at 12 weeks), DoDC, DoSD, DoR, PFS, TTF and OS – Determination of frequency and severity of (serious) adverse events and the number of laboratory values worsening from baseline based on the CTC grade; other safety data (e.g. vital signs and special tests) will be considered as appropriate – Evaluation of the Global Health Status/QoL on the basis of the EORTC QLQ-C30 questionnaire – Exploratory: To analyse tumour tissue biomarkers before the start of the study treat-ment and upon progression: histopathological analyses including qualitative assessments of tumour-infiltrating lymphocytes (TIL) involving the evaluation of regulatory T cells (Treg), CD8, CD20 and immune checkpoint parameters (e.g. PD-L1); additionally, markers like vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and hypoxia inducible factor-1? (HIF-1?) will be evaluated – Exploratory: To analyse blood biomarkers before the start of study treatment, during the treatment period and upon progression: assessment of blood biomarkers, such as hypoxia inducible factor-1? (HIF-1?), vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1) and to evaluate potential correlations of bio-marker expression and clinical out¬comes (response, PFS, OS) – Exploratory (associated separate project): To evaluate the number of non-users and users of the eHealth system CANKADO in the frame of this study and to analyse the absolute and relative dose intensities, the CBR at 24 weeks after start of treatment, the EORTC QLQ-C30 quality of life data and the frequency of (serious) adverse events in the non-user and user group ;Timepoint(s) of evaluation of this end point: Estimation of ORR, DCR (overall and at 12 weeks), DoDC, DoSD, DoR, PFS, TTF and OS | — |
Countries
Germany
Contacts
Public ContactUniv.-Prof. Dr. med. Marcus Schmidt
Universitätsmedizin Mainz
Outcome results
None listed