Study of efficacy and safety of LEE011 in postmenopausal women with advanced breast cancer.

Phase 1

• Conditions: HR+, HER2- advanced breast cancer; MedDRA version: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003084-61-DE
• Lead Sponsor: ovartis Pharma Service AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-12-09
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 650

Inclusion Criteria

1. Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease.
2. Patient is postmenopausal. Postmenopausal status is defined either by:
• Prior bilateral oophorectomy
• Age =60
• Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range
Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status (NCCN Guidelines Version 2.2014). Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression in this trial.

3. Patient has a histologically and/or cytologically confirmed diagnosis
of estrogen-receptor positive and/or progesterone receptor positive
breast cancer by local laboratory.
4. Patient has HER2-negative breast cancer defined as a negative in situ
hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a
negative in situ hybridization (FISH, CISH, or SISH) test is required by
local laboratory testing.
5. Patient must have either:
• Measurable disease, i.e., at least one measurable lesion as per RECIST
1.1 criteria (tumor lesions previously irradiated or subjected to ther
locoregional therapy will only be considered measurable if disease
progression at the treated site after completion of therapy is clearly
documented) or,
• If no measurable disease is present, then at least one predominantly
lytic bone lesion must be present (patients with no measurable disease
and only one predominantly lytic bone lesion that has been previously
irradiated are eligible if there is documented evidence of disease
progression of the bone lesion after irradiation)
6. Patient has an Eastern Cooperative Oncology Group (ECOG)
performance status 0 or 1

Other inclusion criteria as defined by protocol may apply.
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 357
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 293

Exclusion Criteria

1. Patient who received any CDK4/6 inhibitor.
2. Patient who received any prior systemic anti-cancer therapy
(including hormonal therapy and chemotherapy) for advanced breast
cancer.
Note:
• Patients who received (neo) adjuvant therapy for breast cancer are
eligible. If the prior (neo) adjuvant therapy included letrozole or
anastrozole the disease free interval must be greater than 12 months
from the completion of treatment until randomization.
• Patients who received = 14 daysof letrozole or anastrazole for
advanced disease prior to randomization are eligible
• Any prior (neo) adjuvant anti-cancer therapy must be stopped at least
5 half lives or 7 days, whichever is longer, before randomization
3. Patient is currently receiving any of the following medications and
cannot be discontinued 7 days prior to the start of the treatment:
• That are known strong inducers or inhibitors of CYP3A4/5.
• That have a known risk to prolong the QT interval or induce Torsades
de Pointes.
• That have a narrow therapeutic window and are predominantly
metabolized through CYP3A4/5.
• herbal preparations/medications
4. Patient has a concurrent malignancy or malignancy within 3 years of
randomization, with the exception of adequately treated, basal or
squamous cell carcinoma, non-melanomatous skin cancer or curatively
resected cervical cancer.
5. Patient has active cardiac disease or a history of cardiac dysfunction
including any of the following:
• History of angina pectoris, symptomatic pericarditis, or myocardial
infarction within 12 months prior to study entry
• History of documented congestive heart failure (New York Heart
Association
functional classification III-IV)
• Documented cardiomyopathy
• Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as
determined by
Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• History of any cardiac arrhythmias, e.g., ventricular, supraventricular,
nodal
arrhythmias, or conduction abnormality in the previous 12 months.
• On screening, any of the following cardiac parameters: bradycardia
(heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR
interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec.
• Systolic blood pressure >160 or <90 mmHg

Other exclusion criteria as defined by protocol may apply.

Study & Design

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