safety and efficacy of ribociclib (LEE011) in combination with letrozole for the treatment of men and postmenopausal women with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior hormonal therapy for advanced disease
- Conditions
- hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior hormonal therapy for advanced diseaseMedDRA version: 19.0Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003467-19-GR
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 3000
1. Patient is an adult, male or female = 18 years old at the time of informed consent
NOTE: Sexually active males should use a condom during intercourse while taking drug and for 21 days after stopping medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
2. Male or female with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
3. In the case of women, 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
4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
5. 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.
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status = 2
7. Patient has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by local laboratory):
?Absolute neutrophil count = 1.5 × 109/L
?Platelets = 100 × 109/L
?Hemoglobin = 9.0 g/dL
?Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
?INR = 1.5
?Serum creatinine < 1.5 mg/dl or creatinine clearance = 50 mL/min
?In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN.
?Total serum bilirubin < ULN; or total bilirubin = 3.0 × ULN with direct bilirubin within normal range in patients with well-documented Gilbert’s Syndrome
8. Patient must have a 12-lead ECG with the following parameters at screening:
?QTcF interval at screening < 450 msec (using Fridericia’s correction)
?Resting heart rate = 50 bpm
9. Patient must be able to swallow ribociclib and letrozole tablets
10. Patient has signed informed consent obtained before any trial-related activities and according to local guidelines
11. Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures
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 1800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1200
1. Patient has a known hypersensitivity to any of the excipients of ribociclib or letrozole
2. Patient who received any CDK4/6 inhibitor
3.Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted
Note:
?Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) included letrozole or anastrozole the disease free interval must be greater than 12 months from the completion of treatment until study entry.
?Patients who received = 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
?Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic disease must be stopped at least 5 half-lives or 7 days, whichever is longer, before study inclusion.
4. Patient is concurrently using other anti-cancer therapy.
5. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
6. Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 4.03 Grade = 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
7. Patient who has received radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to start of treatment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom = 25% (Ellis R E 1961) of the bone marrow was irradiated.
8. Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer
9. Patient with central nervous system (CNS) metastases unless they meet ALL of the following criteria:
?At least 4 weeks from prior therapy for CNS disease completion (including radiation and/or surgery) to starting the study treatment.
?Clinically stable CNS lesions at the time of study treatment initiation and not receiving steroids and/or enzyme-inducing anti-epileptic medications for the management of brain metastases for at least 2 weeks.
10. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
11. Patient has a known history of HIV infection (testing not mandatory)
12. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
13. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
?History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
?History of documented congestive heart failure (New York
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 safety and tolerability of ribociclib with letrozole in men and postmenopausal women with HR+, HER2- aBC who received no prior hormonal therapy for advanced disease;Secondary Objective: • To assess the clinical efficacy of ribociclib + letrozole measured by Time-to-Progression (TTP) and tumor response by overall response rate (ORR) and clinical benefit rate (CBR).<br>• To assess treatment impact on patient reported outcome (PRO) measured by variations of Functional Assessment of Cancer Therapy – Breast (FACT-B) questionnaire scores<br>;Primary end point(s): Incidence of AEs, Grade 3/4 AEs & SAEs during treatment with ribociclib + letrozole;Timepoint(s) of evaluation of this end point: refer to section 10.4. of the protocol
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Time-to-Progression (TTP) (RECIST 1.1), based on investigators’ assessment<br>• Overall response rate (ORR) as defined by RECIST 1.1 for patients with measurable disease<br>• Clinical Benefit Rate (CBR) as defined by RECIST 1.1 (including patients with CR, PR, SD, NCRNPD >24 weeks)<br>• Patient Reported Outcome (PRO) using FACT-B questionnaire<br>;Timepoint(s) of evaluation of this end point: refer to section 10.5.1 of the protocol