| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| ER-positive/HER2-negative locally advanced or metastatic (stage IV)breast cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
Estrogen receptor positive and HER2-negative cancer
which started in the breast and which now has either reappeared or
has spread to other organs. |
| Tumore positivo al recettore per gli estrogeni e negativo al recettore HER2 che ha avuto origine nel seno e che ora è ricomparso oppure si è diffuso ad altri organi. |
|
| 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 | 10072737 |
| E.1.2 | Term | Advanced breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 determine time to treatment failure (TTF) defined as the time from the date of randomization to the date when the final dose of trial treatment was administered. |
|
| E.2.2 | Secondary objectives of the trial |
•Progression free survival (PFS) based on local investigator assessment by RECIST 1.1.
•Tolerability: adverse events according to CTCAE v4
•Disease control: best overall response of CR or PR, or SD (or non-CR/non-PD in the case of non-measurable disease only) lasting for at least 24 weeks, measured from randomization until first documentation of progressive disease
•Overall survival (OS)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Histologically or cytologically confirmed HER2‐negative locally advanced or metastatic (stage IV) breast cancer.
•Maximun of one prior line of chemotherapy for advanced or metastatic brest cancer
•Measurable or non‐measurable, but radiologically evaluable (except for skin lesions), disease according to RECIST 1.1 criteria.
•Female aged 18 years or older.
•Life expectancy > 3 months.
•Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
•ER‐positive disease by local laboratory, determined on most recent available tissue (latest biopsy of metastatic lesion, otherwise prior biopsy or surgical specimen).
•If previously treated with a taxane in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days).
•Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization.
•Normal hematologic status,
-Absolute neutrophil count ≥1000/mm3
(1.0 × 109/L)
-Platelets ≥ 100 × 109/L
-Hemoglobin ≥ 9 g/dL (≥ 90 g/L)).
•Normal renal function: serum creatinine ≤ 1.5 ULN or calculated creatinine clearance ≥ 50mL/min according to the Cockcroft-Gault formula.
•Normal liver function:
-Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). In the case of known Gilbert’s syndrome, a higher serum total bilirubin (< 3 × ULN) is allowed
-AST and ALT ≤ 3 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN.
•Women of child bearing potential must have documented negative pregnancy test within 2 weeks prior to randomization and agree to acceptable birth control during and up to 6 months after trial therapy.
•Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to starting screening procedures and randomization.
•The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
|
|
| E.4 | Principal exclusion criteria |
•More than one prior line of chemotherapy for advanced or metastatic breast cancer
•More than 2 lines of previous endocrine therapy for locally advanced or metastatic breast cancer.
•Known active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of CNS metastases or spinal cord compression are eligible if they are clinically and radiologically stable for at least 4 weeks before first dose of trial treatment and have not required high-dose steroid treatment in the last 4 weeks).
•Peripheral neuropathy grade 2 or higher (CTCAE version 4.0).
•Significant uncontrolled cardiac disease (i.e. unstable angina, myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure.
•Pregnant or lactating.
•Prior history of non‐breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder).
•Any concurrent condition which in the Investigator’s opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol.
•Contraindications or known hypersensitivity to the trial medication or excipients.
•The use of any anti‐cancer investigational agents within 30 days prior to expected start of trial treatment.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to treatment failure (TTF) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Time from the date of randomization to the date when the final dose of trial treatment was administered. |
|
| E.5.2 | Secondary end point(s) |
- Safety and tolerability
- Disease Control
- Progression free survival (PFS)
- Overall survival (OS) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Safety and tolerability: Adverse events (AE) will be collected using CTCAE v4.0
- Disease Control: Best overall response of complete response (CR) or partial Response (PR), or stable disease (SD) lasting for at least 24 weeks, measured from randomization until first documentation of progressive disease.
- Progression free survival (PFS): Time from randomization until documented disease progression according to RECIST 1.1 criteria or death, whichever occurs first.
- Overall survival (OS): Time from start of trial treatment to death from any cause. |
|
| 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 | Yes |
| 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 | No |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 23 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| LVLS: 24 months patient accrual and 12 months Follow-up after the randomization of the last Patient (36 months). |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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