| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027475 |
| E.1.2 | Term | Metastatic breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the Disease Control Rate (CR + PR + SD in both arms) assessed during study treatments. |
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| E.2.2 | Secondary objectives of the trial |
In both arms:
-To evaluate the Duration of Disease Control
-To evaluate the Disease Control Rate without grade 3-4 toxicity
-To evaluate the Disease Control Rate without grade 3-4 neutropenia
-To evaluate the Objective Response Rate
-To evaluate the Objective Response without grade 3-4 toxicity
-To evaluate the Objective Response without grade 3-4 neutropenia
-To evaluate the Duration of Response
-To evaluate the Time to First Response
-To evaluate the Duration of Stable Disease
-To estimate the Progression-Free Survival
-To estimate the Progression-Free Survival without grade 3-4 toxicity
-To estimate the Progression-Free Survival without grade 3-4 neutropenia
-To estimate the Time To Treatment Failure
-To estimate the Overall Survival
-To estimate the Tolerance
-To estimate the Quality of Life.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Patients must give written (personally signed and dated) informed consent before completing any study-related procedure;
•Absence of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions should be assessed with the patient before randomisation in the trial;
•The patient must have access to social insurance if applicable according to the local regulations;
•Patients > or = 18 years;
•Histologically confirmed adenocarcinoma of the breast;
•Karnofsky Performance status (KPS) > or = 70%;
•Documented locally advanced or metastatic disease previously untreated by chemotherapy and not amenable to curative surgery or radiotherapy;
•Hormone receptor positive disease determined by > or =1% positive stained cells for estrogen and/or progesterone receptor by immunohistochemistry on the primary tumor or on metastatic site;
•HER2 negative (assessed by 0-1+ IHC or 2+ IHC with FISH or CISH negative) on the primary tumor or on metastatic site;
•Patients should have progressed to at least one previous hormone therapy for breast cancer at any stage of the disease and/or should be considered as no longer candidates to further hormone therapy;
•Patients who have received adjuvant or neoadjuvant chemotherapy are allowed if the interval between the end of chemotherapy and the date of registration in the trial is superior to 12 months;
•Complete staging within 4 weeks prior to randomisation;
•Presence of at least one measurable lesion which has not been previously irradiated (RECIST criteria. Version 1.1). Measurable lesions (measured in at least one dimension, longest diameter to be recorded) as > or = 20 mm with conventional techniques or as > or = 10 mm with CT scan. Physical examination and ultrasound will not be considered as objective tumour assessments;
•Women of childbearing potential must be using a medically accepted method of contraception to avoid pregnancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment in such a manner that the risk of pregnancy is minimised;
•Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study treatment;
•Fertile men must be using an effective method of birth control if their partners are women of childbearing potential throughout the study period and for up to 3 months after the last dose of study treatment;
•Patients may have received prior radiotherapy but a minimum of a 4 weeks interval must have elapsed;
•Life expectancy > or = 16 weeks;
•Adequate bone marrow, hepatic and renal functions as evidenced by the following:
-Haemoglobin > or = 10 g/dL
-Absolute Neutrophil Count > or = 1.5 x 109/L
-Platelet Count > or = 100 x 10^9/L
-Total Bilirubin < 1.5 x ULN (ULN: Upper Limit of Normal)
-SGOT/SGPT < or = 2.5 x ULN
-Alkaline phosphatase < 5 x ULN
-Creatinine Clearance > 40 mL/min, calculated using the Cockroft and Gault formula.
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|
| E.4 | Principal exclusion criteria |
•Female is not eligible to enter the study if :
-pregnant or lactating
-with positive pregnancy test at inclusion;
•Patients with symptoms suggesting CNS involvement or leptomeningeal metastases;
•Concomitant hormonal therapy for advanced breast cancer;
•Malabsorption syndrome or disease significantly affecting gastro-intestinal function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine;
•Prior treatment with chemotherapy in the locally advanced or metastatic setting;
•Patients with dysphagia, or inability to swallow the tablets;
•Other serious illness or medical conditions:
-Clinically significant cardiac disease
-Unstable diabetes
-Uncontrolled hypercalcemia
-Clinically significant active infections (current or in the last two weeks)
-Previous organ allograft;
•Current peripheral neuropathy > or = grade 2 according to NCI version 4.0 criteria;
•Participation in another clinical trial with any investigational drug within 30 days prior to randomisation and/or during the study;
•History of another malignancy within the past five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix;
•Known hypersensitivity to vinca alkaloids. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Disease Control Rate (CR + PR + SD in both arms) assessed during study treatments in both arms |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Tumour assessments will be performed according to the RECIST guidelines (version 1.1). Assessments will be carried out at baseline and every 6 weeks until disease progression. |
|
| E.5.2 | Secondary end point(s) |
in both arms;
-To evaluate the Duration of Disease Control
-To evaluate the Disease Control Rate without grade 3-4 toxicity
-To evaluate the Disease Control Rate without grade 3-4 neutropenia
-To evaluate the Objective Response Rate
-To evaluate the Objective Response without grade 3-4 toxicity
-To evaluate the Objective Response without grade 3-4 neutropenia
-To evaluate the Duration of Response
-To evaluate the Time to First Response
-To evaluate the Duration of Stable Disease
-To estimate the Progression-Free Survival
-To estimate the Progression-Free Survival without grade 3-4 toxicity
-To estimate the Progression-Free Survival without grade 3-4 neutropenia
-To estimate the Time To Treatment Failure
-To estimate the Overall Survival
-To estimate the Tolerance
-To estimate the Quality of Life.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumour assessments will be performed according to the RECIST guidelines (v 1.1). Assessments will be carried out at baseline and every 6 weeks until disease progression.
Clinical safety will be assessed by:
-complete history of malignant and non malignant disease
-full physical examination including vital signs, weight, PS
-regular reporting of AEs that will be graded by using NCI/CTC grading v 4.0.
-complete blood cell counts on a weekly basis
-serum chemistry at baseline then on day 1 of each cycle
The EORTC QLQ-C30 V 3.0 quality of life questionnaires will be filled in at baseline before randomisation, then immediately before cycle 2, cycle 4, cycle 6 etc… and at the end of study treatment. Changes of the scores from baseline of the parameters will be provided from baseline. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Same medicinal product with different posology |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study period is defined as the date of last progression observed in the study. The follow-up period is the time from 30 days after the last study treatment administration until death. Survival information will be collected approximately every 6 weeks until progression of the disease and then every 3 months until death or decision for study closure. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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