A Phase IV Study to Collect Data on the Efficacy and Safety of RIBociclib in Older Women With Breastcancer

Study Overview
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Brief Summary
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The RibOB study is a prospective, open lable, single arm trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (≥70 years) with HR+/HER2- aBC and no prior hormonal treatment for advanced disease (as per approved indication).

Detailed Description
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The RibOB study is an observational prospective, open lable single arm phase IV trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (≥70 years) with HR+, HER2- advanced breast cancer and no prior hormonal treatment for advanced disease as per the indication approved by the European Medicines Authority (EMA) and as made available by Belgian national authorities in the national health care system. A total of maximum 150 patients will be enrolled for treatment with Letrozole (2.5 mg once daily) + ribociclib 600 mg (day 1 to 21 in a 28 day cycle), which will continue until disease progression, intolerable toxicity or patient/physician decision to withdraw. During the study, patients will be continuously evaluated for disease progression as per national standard of care (approximately every 12 weeks radiologically); for safety; and for quality of life and geriatric assessment components including functional status with QoL assessment and CGA at 3 months (+/- 2 weeks) and at 1 year (+/-2 weeks).

Official Title
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A Phase IV Study to Collect Data on the Efficacy and Safety of RIBociclib With Letrozole in Older Women (≥70 Years) With HR+ and HER2- Advanced Breast Cancer (aBC) With no Prior Systemic Therapy for Advanced Disease.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ribociclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is a female ≥ 70 years old at the time of informed consent. Advanced breast cancer (defined as locoregionally recurrent or metastatic not amenable to curative therapy). Histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory (defined as ER and/or PgR ≥1% or Allred >2). 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 as determined by local laboratory testing according to ASCO-CAP guidelines is necessary. Patient has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by local laboratory), preferably tested a maximum of 14 days before enrolment: Patient has signed informed consent obtained before any trial-related activities and according to local guidelines. Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures. Exclusion Criteria: Patient has a known hypersensitivity to any of the excipients of ribociclib or letrozole. Patients who received any CDK4/6 inhibitor previously. Patient who received any prior systemic antihormonal therapy or chemotherapy for advanced breast cancer. Patient is concurrently using other systemic anti-cancer therapy (except bone modifying agents). Patient with central nervous system (CNS) metastases and/or documented meningeal carcinomatosis unless they meet ALL 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 (radiological confirmation of brain disease status is not necessary). 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.). Patients who already have or who are at significant risk of developing QTc prolongation are not eligible for the study. This includes patients: with long QT syndrome; with uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmias; with electrolyte abnormalities (potassium, magnesium, sodium and calcium) that are NCI CTCAE 4.03 grade 2 or higher (for details, see table 10 ). Note: phosphate testing is not mandatory, but should the investigator consider measuring it before enrolment, the same rules may be applied

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ribociclib|combination of ribociclib and letrozole|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Clinical efficacy: Progression-free survival (PFS) (defined as the length of time from the start of treatment and death or progression of disease) as determined by the local investigator using RECIST 1.1 rules. | 2018-2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure (TTF) | Efficacy: Time to treatment failure (TTF). It is defined as time from date of start of treatment to the date of event defined as the first documented progression, death due to any cause or withdrawal from treatment. | 2018-2022 | 
| Overall response rate (ORR) | Efficacy: Overall response rate (ORR), for patients with measurable disease as determined locally by investigator according to RECIST 1.1. It is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. | 2018-2022 | 
| Overall Survival (OS) | Efficacy: Overall survival (OS). It is defined as the length of time from the start of treatment and death from any cause. | 2018-2022 | 
| Breast cancer specific survival (BCSS) | Efficacy: Breast cancer specific survival (BCSS). It is defined as the length of time from the start of treatment and death from breast cancer. | 2018-2022 | 
| Adverse events | Safety: Incidence of Adverse Events according to the NCI-CTCAE 4.03 during study treatment and according to the results of baseline CGA evaluation; Number of patients who stop ribociclib before progression ; number of patients needing dose interruption/reduction. | 2018-2022 | 
| Treatment discontinuation | Safety: Number of patients who stop ribociclib before progression | 2018-2022 | 
| Treatment interruption | Safety: number of patients needing dose interruption | 2018-2022 | 
| Treatment reduction | Safety: number of patients needing dose reduction | 2018-2022 | 
| PFS / OS | Prediction Modeling I: PFS and OS prognostic model based on clinical/pathologic characteristics | 2018-2022 | 
| CGA / QoL | Prediction Modeling II: Baseline CGA and QoL and relation with PFS/OS | 2018-2022 | 
| Quality of Life (1) | Evolution of QoL during study treatment: EORTC QLQ-C30 (modified) and EORTC IL15 questionnaires | 2018-2022 | 
| Quality of Life (2) | Correlation of baseline QoL with OS | 2018-2022 | 
| Quality of Life (3) | Correlation of baseline QoL with toxicity grade III-IV | 2018-2022 | 
| Comprehensive Geriatric Assessment | Evolution of CGA during study treatment | 2018-2022 | 
| Plasma Biomarker Research (1) | Evolution of potential aging biomarkers during study treatment, and predictive value of baseline aging biomarkers on toxicity, PFS and OS (correcting for the prognostic metastatic index in PFS / OS) | 2018-2022 | 
| Plasma Biomarker Research (2) | Predictive capacity of thymidine kinase on toxicity, PFS, OS and RR (correcting for the prognostic metastatic index in PFS, OS and RR). Thymidine kinase d1 versus d15 drop, and Thymidine kinase d15 level | 2018-2022 | 
| Plasma Biomarker Research (3) | Develop a plasma microRNA signature for response to study treatment (pre-dose cycle 3) | 2018-2022 | 
| Plasma Biomarker Research (4) | Evaluation of plasma antitumor immunity induction by study treatment at day 15 of cycle 1. | 2018-2022 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, elderly, geriatric assessment, geriatric oncology, translational research, biomarkers