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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ribociclib; Drug: letrozole

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Sedona, Arizona, United States, 86336
      • Arizona Oncology Associates PC HAL
  • California
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group SC
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Oncology Speciialists of Charlotte
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Center for Cancer Treatment and Research
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Blood and Cancer Care of South Carolina
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth St Joseph Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ribociclib + letrozole; ribociclib with letrozole per the core study	Drug: Ribociclib; ribociclib + letrozole; Drug: letrozole; ribociclib + letrozole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2017
• Primary Completion (Actual): March 8, 2019
• Study Completion (Actual): March 8, 2019

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (Actual): February 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Phase III; LEE011; ribociclib; Premenopausal; Men; letrozole; Postmenopausal; CDK4/6; HER2-negative; Advanced breast cancer; CDK4; CDK6; CDK; Phase IIIb; ER-positive; PR-positive; CDK4/6 inhibitor; HR-positive; femara
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: CLEE011AUS42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No