Treatment with Letrozol and Palbociclib combination in early Breast Cancer HR(+) / HER2(-)

Phase 1

• Conditions: Early HR(+)/HER2(-) Breast Cancer; MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001702-28-ES
• Lead Sponsor: Medica Scientia Innovation Research (MEDSIR)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-25
• Study Completion: 2020-10-29
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 67

Inclusion Criteria

1.Female patients over 18 years of age.
2.Patients have been informed about the nature of study, have agreed to participate in the study, and have signed the informed consent form prior to participation in any study-related activities.
3.Premenopausal and postmenopausal women. Premenopausal women must be treated with LHRH analogue since patient pre- registration. Premenopausal or postmeno-pausal status should have been established before starting study treatment with letrozole plus palbociclib based on the following classification:
a)Postmenopausal status is defined as either:
oPrior bilateral oophorectomy;
Or
oAge>60 years;
Or
oAge<60 years and amenorrhoeic for 12 months in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression, and follicle-stimulating hormone (FSH) and estradiol in postmenopausal range.
b)Premenopausal status is defined as all those women who do not meet any of above criteria.
4.Eastern Cooperative Oncology Group (ECOG) performance status = 1.
5.HR-positive (estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive) EBCs (breast cancers that have at least 1% of cells staging positive for ER and PgR should be considered ER-positive and PgR-positive according to the National Compre-hensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) guide-lines). ER and/or PgR status must be centrally confirmed by using immunohistochemistry (IHC) testing and Allred score of 6-8.
6.Patients with HER2-negative breast cancer through in situ hybridization test (fluores-cence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver en-hanced in situ hybridization [SISH]) or negative immunohistochemical status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required. HER2 status must be centrally confirmed.
7.Ki67 levels = 20% confirmed by IHC testing in a central laboratory.
8.Tumor size >2,0 cm (T2-4 according to TNM staging system, but always >2,0 cm).
9.Limited node involvement (N0-2, according to TNM staging system), as assessed by a sentinel lymph node biopsy, an axillary dissection, or both, and as defined by the Sixth Edition of the American Joint Committee on Cancer (AJCC) staging criteria.
10.No metastatic disease (M0, according to TNM staging system).
11.Available pre-treatment tissue sample (biopsy) material (formalin- fixed paraffin-embedded (FFPE)) for RS central evaluation by the Assay.
12.Patients agree to collection of tissue biopsy from the primary breast cancer at the time of study inclusion (screening), at Cycle 1 Day 14 of treatment, and after 24 weeks, or if experience intolerable side effects, disease progression, or withdraw during 24 weeks of study treatment.
13.Patients must have biopsable and measurable disease (according to RECIST criteria v.1.1).
14.No prior chemotherapy, endocrine or radiation therapy for current disease.
15.Adequate organ function:
a)Hematological: White blood cell (WBC) count = 3.0 x 109/L, absolute neutrophil count (ANC) = 1.5x 109/L, platelet count = 75.0 x109/L, and hemoglobin = 10.0 g/dL (= 6.2 mmol/L).
b)Hepatic: Bilirubin = 1.5 times the upper limit of normal (x ULN) (or total bilirubin = 3.0 x ULN or direct bilirubin = 1.5 x ULN in patients with well-documented Gilbert's syndrome); alkaline phosphatase (ALP) = 2.5 times ULN; aspartate transaminase (AST) and alanine transami-nase (ALT) = 3 times ULN.
c)Renal: Serum creatinine = 1.5

Exclusion Criteria

1.Metastatic progression (M1, according to TNM staging system).
2.Substantial nodal involvement (N>2, according to TNM staging system).
3.Non-large tumor (T0-1, according to TNM staging system).
4.Bilateral breast carcinoma.
5.Inflammatory carcinoma (T4d, according to TNM staging system).
6.Patients with exclusive non-measurable/evaluable disease.
7.Known hypersensitivity to any palbociclib excipients.
8.Known hypersensitivity to any letrozole excipients.
9.Formal contraindication to endocrine therapy.
10.Patients unable to swallow tablets.
11.Other malignancies within the past five years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix.
12.Previous radiotherapy on the ipsilateral chest wall for the treatment of any other malignance.
13.Major surgery (defined as requiring general anesthesia) or significant traumatic injury within four weeks of start of study treatment, or patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the course of the study.
14.Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).
15.Patients with an active bleeding diathesis, previous history of bleeding diathesis, or anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention).
16.History of malabsorption syndrome or other condition that would interfere with enteral absorption.
17.Chronic daily treatment with corticosteroids with a dose of = 10 mg/day methylpredniso-lone equivalent (excluding inhaled steroids).
18.QTc interval > 480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
19.Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (i.e., hypocalcemia, hypokalemia, or hypomagnesemia).
20.Participation in the treatment phase of an interventional trial within 30 days prior to study treatment start.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified