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• Register: EUCTR
• Last refreshed on: 15 September 2020
• Main ID: EUCTR2014-002560-33-BE
• Date of registration: 24/04/2015
• Prospective Registration: Yes
• Primary sponsor: UNICANCER
• Public title: _
• Scientific title: Open-label, randomized, multicenter, international, parallel exploratory phase II study, comparing 3 FEC-3 Docetaxel chemotherapy to letrozole + palbociclib combination as neoadjuvant treatment of stage II-IIIA PAM 50 defined Luminal breast cancer, in postmenopausal women. - NEOPAL
• Date of first enrolment: 16/06/2015
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002560-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Standard chemotherapy; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France

Contacts

• Name: Hélène MANDUZIO, project leader
• Affiliation: UNICANCER

• Name: Hélène MANDUZIO, project leader
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
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) PAM50 (Prosigna™) centralized evaluation available and:
- Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B for randomized patients PAM50.
- Or Luminal A N- for non-randomized patients.
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

Exclusion criteria:
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) Diagnosis of hypokalemia

9)History of any previous anti-cancer chemotherapy and any previous treatment using AI
10) Concurrent administration of herbal preparations as complementary medicine.
11) 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
12) 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Post-menopausal patients with localized, stage II-IIIA, candidate for chemotherapy but not candidate or uncertain for breast conservation, PAM50 (Prosigna™)- defined Luminal A and Node-positive or Luminal B (ER+ and HER2-) operable breast cancer (randomized cohort), or Luminal A N- (non randomized cohort).
MedDRA version: 20.0 Level: LLT Classification code 10006190 Term: Breast cancer invasive NOS System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Palbociblib
Product Code: PD-0332991
Pharmaceutical Form: Capsule
INN or Proposed INN: PALBOCICLIB
Other descriptive name: PALBOCICLIB
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 75-125

Trade Name: FEMARA
Pharmaceutical Form: Coated tablet
INN or Proposed INN: LETROZOLE
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Fluoro-uracile
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: FLUOROURACIL
Other descriptive name: FLUOROURACIL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: EPIRUBICINE
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: EPIRUBICIN
Other descriptive name: EPIRUBICIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: ENDOXAN
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 500-1000

Trade Name: DOCETAXEL
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOCETAXEL
Other descriptive name: DOCETAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 10-40

Primary Outcome(s)

Main Objective: To evaluate the ability of each treatment strategy to provide RCB 0-I pathological tumor response at surgery (local assessment) in luminal A N+ and luminal B patients subgroup.

Secondary Objective: 1. EFFICACY:
- To evaluate clinical responses in each arm and in each subgroups (luminal A N+ and luminal B; luminal A N-), as defined by clinical and US examination.
- To evaluate the rates of breast conservation therapy according to each treatment scheme.
-- To evaluate the progression free survival (PFS) and invasive disease free survival (iDFS) at 3 years follow-up;
- To evaluate RCB 0-1 pathological tumor response by central pathology reading.
2. TOXICITY
- To assess the safety of each treatment strategy.
3. BIOLOGY
- To assess the positive predictive value of ROR on clinical and pathological tumor response in both treatment arms.
- 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.

Primary end point(s): Local RCB rates in the two arms of the study in Luminal A N+ and Luminal B patients.

Timepoint(s) of evaluation of this end point: _

Secondary Outcome(s)

Secondary end point(s): • Clinical/radiological response rates in each treatment arm (RECIST 1.1)
• Safety (CTC-AE V4.0)
• Relative dose intensity of each drug in both arms
• Positive and negative predictive values of PAM50 ROR-defined status in both arms
• Assessment of several biomarkers as potential predictors of clinical and pathological response in both arms
• Central RCB rates
• Rates of BCS in the two arms, with regard to the initially planned surgery
In Luminal A N- patients: ?
• Clinical/radiological response rates (RECIST 1.1) ?
• Safety (CTC-AE V4.0) ?
• Central RCB rates ?
• Rates of BCS with regard to the initially planned surgery

Timepoint(s) of evaluation of this end point: _

Secondary ID(s)

2014-002560-33-FR

UC-0140/1404_CARMINA04

Source(s) of Monetary Support

Pfizer Laboratories

Ethics review

Status: Approved
Approval date: 16/06/2015
Contact: