HR-positive/HER2-negative metastatic breast cancer.
Conditions
Interventions
Trade Name: Kisqali 200 mg
Product Name: Ribociclib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIBOCICLIB
Concentration unit: mg milligram(s)
Concentration number: 200-
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements. 2. Female patients. 3. Age = 18 years old. 4. Histologically confirmed HER2-/HR+ locally advanced or metastatic invasive breast carcinoma assessed on the primary tumor and/or on the metastatic lesions (preferred). 5. Willingness and ability to provide archived formalin fixed paraffin embedded tissue block or a partial block from primary surgery and/or tumor or metastasis biopsy, which will be used for further breast cancer research. 6. Maintenance endocrine therapy could have already been started up to 6 weeks before enrolment, but after achievement of tumor response or stable disease. 7. Maintenance therapy must be preceded prior to enrolment by at least 4 cycles of a mono- or polychemotherapy. Tumor response or stable disease needs to be maintained to allow entry into the trial. Study treatment must start within 8 weeks of the last dose of chemotherapy. 8. Previous therapy with maximum one line of anti-hormonal treatment is allowed. 9. Previous neoadjuvant/adjuvant therapy is allowed. In case of cancer other than breast cancer, treatment should be completed more than 5 years before study entry. 10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 11. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures 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). 12. The patient must be accessible for scheduled visits, treatment and follow-up. Patients registered on this trial must be treated at the participating center which could be the Principal or a Co- investigator’s site. 13. Life-expectancy > 6 months. 14. The subjects need to be either A) of non-childbearing potential (documented postmenopausal or post hysterectomy) or B) childbearing potential with negative urinary pregnancy test (in this case patients need to use highly effective non-hormonal contraceptive). 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 95 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: 1. Uncontrolled/untreated central nervous system lesions. 2. Known severe hypersensitivity reactions to compounds similar to one of the investigational and supportive treatment. 3. Inadequate organ function immediate prior to randomization including: ?- Hemoglobin 2.0 x upper normal limits (ULN) ?- Alkaline phosphatase (ALP) > 2.5 x ULN ?- Total serum bilirubin > 1.5 x ULN ?- Serum creatinine >1.5 x ULN or estimated creatinine clearance 450 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes. 8. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (i.e. hypocalcemia, hypokalemia, hypomagnesemia). 9. Any of the following within 6 months prior to enrolment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 grade = 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. 10. Other severe acute, uncontrolled or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 11. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry. 12. Patients treated within the last 7 days prior to enrolment with drugs known to be CYP3A4 inhibitors or inducers (see section 11.4) or drugs that are known to prolong the QT interval. 13. Pregnant and lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the median PFS with 95% confidence interval (CI) of an anti-hormonal maintenance therapy after 1st line chemotherapy at the discretion of the investigator (e.g. taxanes, capecitabine, vinorelbine, anthracycline) with the CDK4/6 inhibitor ribociclib.;Secondary Objective: - To determine the overall survival rate at seven months - To describe safety, treatment compliance and clinical benefit rate - To evaluate patient reported outcomes ;Primary end point(s): Locally-assessed progression-free survival (PFS) defined as the time elapsed between enrolment and tumor progression or death from any cause.;Timepoint(s) of evaluation of this end point: 7 months after last subject enrolled (after end of study) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: - Overall survival (OS) defined as the time elapsed between treatment enrolment and death from any cause - Clinical benefit rate (CBR) defined as the proportion of subjects with best response of complete response, partial response, or stable disease for at least 24 weeks. Safety will be assessed on the basis of adverse events, serious adverse events and adverse events of special interest. Safety by toxicity grades is defined by the NCI-CTCAE version 4.03. Compliance will be assessed on the basis of treatment reductions, interruptions and permanent discontinuations with reasons. Quality of life (QoL) will be assessed using the General Quality of Life questionnaire (FACT-B), which will be filled in at study entry and every three month thereafter. ;Timepoint(s) of evaluation of this end point: All secondary endpoints, will be assessed at the same timepoints as the primary endpoint. | — |
Countries
Germany
Contacts
Public ContactAMICA
GBG Forschungs GmbH
Outcome results
None listed