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- Conditions
- Post-menopausal patients with localized, stage II-IIIA, PAM50 ROR (Prosigna™)- defined Luminal A and Node-positive or Luminal B (ER+ and HER2-) operable breast cancer, candidate for chemotherapy but not candidate or uncertain for breast conservation.MedDRA version: 17.1Level: LLTClassification code 10006190Term: Breast cancer invasive NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002560-33-FR
- Lead Sponsor
- ICANCER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 180
1) Aged = 18 years, Post-menopausal women according to the following criteria
Age > 60 years,
Bilateral ovariectomy,
Age = 60, with an uterus and presenting an amenorrhea of more than 12 months,
Age = 60 without an uterus and FSH > 20 IU/L
2) Newly diagnosed and operable unilateral invasive breast cancer, not candidate or uncertain for breast conservation –
Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all share the same characteristics: ER Allred 4, Her2- (PAM50 will be performed in the largest lesion)
3) Stage II-IIIA
4) Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)
5) Non metastatic, M0
6) ER-positive by IHC (Allred Score=4)
7) HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish
8) Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation
9) ECOG 0-1
10) No prior systemic therapy for the present tumor
11) Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria:
o Absolute Neutrophil Count (ANC) =1,500/mm3 or =1.5 x 10^9/L
o Platelets =100,000/mm3 or =100 x 10^9/L
o Hemoglobin =9 g/dL
o Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) =2.5 x upper limit of normal (ULN)
o Alkaline phosphatase =2.5 x ULN
o Total serum bilirubin =1 x ULN
o Serum creatinine =1.5 x ULN or estimated creatinine clearance = 60 mL/min as calculated using the method standard for the institution
12) Adequate cardiac functions, including:
o 12 Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention.
o QTc interval =480 msec
o No history of Torsades de Pointes or other symptomatic QTc abnormality.
13) Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
14) Signed informed consent and health insurance coverage
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120
1) Non operable, bilateral, T4 or metastatic breast cancer
2) Limited T2 breast cancer immediately accessible to conservative surgery
3) Previous homolateral breast cancer (including in situ carcinoma), and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment
4) Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
5) Previous use of SERMs such as raloxifene
6) Any surgery (not including minor procedures such as lymph node biopsy, primary tumor core biopsy, fine needle aspiration) within 4 weeks of start of study treatment; or not fully recovered from any side effects of previous procedures.
7) Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
8) History of any previous anti-cancer chemotherapy and any previous treatment using AI
9) Concurrent administration of herbal preparations as complementary medicine.
10) Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs, such as the inability to take oral medication in tablet form and malabsorption syndrome
11) Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the ability of each treatment strategy to provide RCB 0-I pathological tumor response at surgery;Secondary Objective: 1. EFFICACY:<br>- To evaluate clinical responses in each arm, as defined by clinical and US examination.<br>- To evaluate the rates of breast conservation therapy according to each treatment scheme. <br>2. TOXICITY<br>- To assess the safety of each treatment strategy. <br>3. BIOLOGY<br>- To assess the positive predictive value of ROR on clinical and pathological tumor response in both treatment arms.<br>- To evaluate the ability of predefined biomarkers to predict for clinical and pathological response in each arm, such as p53 mutation status, RB and CCND1 status, as well as other proliferation and senescence biomarkers.<br>;Primary end point(s): RCB rates in the two arms of the study;Timepoint(s) of evaluation of this end point: _
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Clinical/radiological response rates in each treatment arm (RECIST 1.1)<br>• Safety (CTC-AE V4.0)<br>• Relative dose intensity of each drug in both arms<br>• Positive and negative predictive values of PAM50 ROR-defined status in both arms<br>• Assessment of several biomarkers as potential predictors of clinical and pathological response in both arms<br>• Rates of BCS in the two arms, with regard to the initially planned surgery;Timepoint(s) of evaluation of this end point: _