metastatic/recurrent breast cancer with Hormone receptor positive and HER2 negative metastatic breast cancer, hormone receptor positive, HER2 negative, Ribociclib
Conditions
Interventions
Ribociclib 400mg/day and 600mg/day (phase1b)
Ribociclib 600mg/day (phase2)
Sponsors
Iwata Hiroji
Nozawa Kazuki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Participant has a histologically and/or cytologically confirmed diagnosis of estrogenreceptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory 2.Participant has evidence of recurrence or progression on or after the last systemic therapy prior to enrollment 3.Age 18 years or older on the date of enrollment. 4.Performance status (PS) is 0 or 1 according to ECOG criteria (PS must be documented in the medical record). 5.Participant has HER2-negative breast cancer defined as a negative in situ hybridization (ISH) test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (such as FISH, CISH, SISH or DISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample 6.Phase Ib part: with or without measurable lesions. 7.Phase2 part: Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1. (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation). 8.No active brain metastases requiring treatment 9.Participant is pre/peri and postmenopausal. Postmenopausal status is defined either by: Prior bilateral oophorectomy, Age >=60, Age = 1.5 x 109/L Platelets >= 100 x 109/L Hemoglobin >= 9.0 g/dL Modification of Diet in Renal Disease (MDRD) formula. Total bilirubin < ULN except for participants with Gilbert's syndrome who may only be included if the total bilirubin is =< 3.0 x ULN or direct bilirubin =< 1.5 x ULN. Aspartate transaminase (AST) < 2.5 x ULN, except for participants with liver metastasis, who are only included if the AST is < 5 x ULN. Alanine transaminase (ALT) < 2.5 x ULN, except for participants with liver metastasis, who are only included if the ALT is < 5 x ULN Participant must have the following laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication: Potassium Magnesium Total Calcium (corrected for serum albumin) 11.Standard 12-lead ECG values as assessed by central laboratory (triplicate ECGs if applicable) QTcF interval at screening < 450 msec (QT interval using Fridericia's correction) Mean resting heart rate 50-90 bpm (determined from the ECG) 12.Must be able to swallow ribociclib 13.Patients with a life expectancy of 3 months or more 14.Confirmed negative serum pregnancy test (beta-hCG) 14 days prior to enrollment or before starting study treatment or participant has had a hysterectomy in pre/peri menopausal patients and must be willing to use highly effective methods of contraception in childbearing potential or pre-menopausal patients 15.Signed informed consent must be obtained prior to participation in the study.
Exclusion criteria
Exclusion criteria: 1.Participant with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment 2.Patients receiving chemotherapy as treatment for metastasis or recurrence (excluding preoperative and postoperative chemotherapy) and patients who have used CDK4/6 inhibitors (excluding use in preoperative and postoperative settings) 3.Participant has a concurrent malignancy or malignancy within 2 or 3 years of enrollemnt, with the exception of adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ. 4.Participant with a known hypersensitivity to any of the excipients of ribociclib (e.g., rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose galactose malabsorption, and soy allergy) 5.Participant is concurrently using hormone replacement therapy 6.Participant has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. 7.Participant has not recovered from clinical, and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade == 25% of the bone marrow has been previously irradiated are also excluded. 9.Participants with central nervous system (CNS) involvement unless they meet ALL of the following criteria: At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment. Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases. 10.Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 11.Participant has a known history of HIV infection (testing not mandatory) 12.Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including but not limited to any of the followingHistory of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry Documented cardiomyopathy Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following 13.Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade A
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase1b part: Tolerability Phase2 part: Overall response rate (ORR) by central review | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase1b part: pharmacokinetics (PK), adverse events (AE), serious advese events (SAE) Phase2 part: Progression Free Survival (PFS), Overall Survival (OS), Percentage of adverse events, ORR by investigator | — |
Contacts
Public ContactHiroji Iwata
Nagoya City University
Outcome results
None listed