A Companion Sample Collection Protocol to Support the Discovery of Breast Cancer Aberrations With Treatment of CDK4/6 Therapy/LEE011/Ribociclib

Study Overview
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Brief Summary
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This study was a companion study to CLEE011A2404 which provided the opportunity for the collection of tumor tissue samples to better understand relevant mutations and the mechanisms responsible for resistance to treatment.

Detailed Description
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This was a multicenter, non-treatment based companion sample collection protocol conducted in the US only. This protocol sought to evaluate the aberrations of common pathways for newly diagnosed HR+/HER2- advanced breast cancer tumors and responses to ribociclib in diverse patient populations. This companion sample collection protocol was available for all US patients enrolled on CLEE011A2404 (CompLEEment-1) and did not alter the planned treatment. Tumor collection required for this study occurred at two time points: at baseline/screening and upon the development of progressive disease as shown in the protocol. Patients eligible for this companion study were required to sign an optional additional consent form at the time of enrolling into the core trial. After eight patients had consented and samples had been taken, it was determined that the companion study protocol had not been properly initiated or monitored at the sites. This was determined to be a significant GCP violation and the clinical team made the decision to terminate the trial. In addition to the GCP issues, enrollment had been closed to the core study so enrolling additional patients was no longer possible. The limited number of samples would not provide any meaningful analysis. The samples were never analyzed. The study was not terminated due to safety or efficacy concerns. Samples collected were either destroyed or will be retained for up to 15 years based upon the decision of the patient.

Official Title
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A Companion Sample Collection Protocol to Support the Discovery of Breast Cancer Aberrations With Treatment of CDK4/6 Therapy/LEE011/Ribociclib

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ribociclib
* Drug: letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent was to have been obtained prior to any baseline/screening procedures. Patients eligible for this companion sample collection protocol sample collection protocol must have met all inclusion in CLEE011A2404. Exclusion Criteria: Patients eligible for this companion sample collection protocol must not have met any of the exclusion criteria in the CLEE011A2404 study, in addition to the following: Patients without either fresh or archival tumor tissue accessible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ribociclib + letrozole<br>ribociclib with letrozole per the core study | Drug: Ribociclib<br>* ribociclib + letrozole<br>Drug: letrozole<br>* ribociclib + letrozole<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify Mutations of Genes From Tissue Samples Between Baseline and Time to Progression to Determine Modes of Resistance to Ribociclib After Disease Progression | Mutations of genes that were relevant to HR+ and the CDK4/6 pathway such as but not limited to CCND1, CDKN2A, PIK3CA and PTEN to identify the potential mechanisms of progression. | Baseline, time of progression approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the Differences in Mutations Across Various Races / Ethnicities Based on Baseline Samples | Change in mutations would have been assessed based on baseline samples and compared across diverse races/ethnicities with HR+ HER2- advanced breast cancer - specifically Caucasian, African America, Hispanic, Native American and Pacific Islander. | Baseline, time of progression approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HR-positive, HER2-negative, Advanced breast cancer, LEE011, ribociclib, letrozole, femara, CDK, CDK4, CDK6, CDK4/6, CDK4/6 inhibitor, Phase III, Phase IIIb, ER-positive, PR-positive, Postmenopausal, Premenopausal, Men