Breast Cancer
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGRibociclib
ribociclib + letrozole
DRUGletrozole
ribociclib + letrozole
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identify Mutations of Genes From Tissue Samples Between Baseline and Time to Progression to Determine Modes of Resistance to Ribociclib After Disease Progression | Baseline, time of progression approximately 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Differences in Mutations Across Various Races / Ethnicities Based on Baseline Samples | Baseline, time of progression approximately 24 months | 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. |
Countries
United States
Participant flow
Recruitment details
All patients had to have met all eligibility criteria and to have been enrolled into the CLEE011A2404 core study. Patients were offered the opportunity to consent and enroll into this optional companion study.
Participants by arm
| Arm | Count |
|---|---|
| Ribociclib + Letrozole ribociclib with letrozole | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated by sponsor | 8 |
Baseline characteristics
| Characteristic | Ribociclib + Letrozole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race/Ethnicity, Customized Black | 2 participants |
| Race/Ethnicity, Customized Caucasian | 6 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: Baseline, time of progression approximately 24 months
Population: No samples were analyzed
Secondary
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.
Time frame: Baseline, time of progression approximately 24 months
Population: No samples were analyzed