LEE011 For Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

Study Overview

LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

The purpose of this signal seeking study was to determine whether treatment with LEE011 demonstrates sufficient efficacy in CDK4/6 pathway activated solid tumors and/or hematologic malignancies to warrant further study.

N/A

Tumors With CDK4/6 Pathway Activation

DRUG: LEE011

CLEE011XUS03

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-07-09	Results First Submitted 2019-01-16	Last Update Submitted that met QC Criteria 2019-07-16
First Submitted that Met QC Criteria 2014-07-09	Results First Submitted that Met QC Criteria 2019-04-12	Last Update Posted (ACTUAL) 2019-07-18
First Posted (ACTUAL) 2014-07-11	Results First Posted 2019-04-16	Last Verified 2019-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: LEE011 LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.	DRUG: LEE011 Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: LEE011

LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.

DRUG: LEE011

Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments	Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS	Baseline up ≥16 weeks up to approximately 36 months
Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS	CBR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR + PR + SD for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm FAS	Baseline and ≥ 16 weeks up to approximately 36 months
Overall Response Rate (ORR) ≥ 16 Weeks. FAS	ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS	Baseline and ≥ 16 weeks up to approximately 36 months

Secondary Outcome Measures	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression-free survival (PFS) is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a subject has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progressive disease is defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression)	Every 8 weeks until death, assessed up to 24 months
Overall Survival (OS)	Number of participants Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.	Baseline up to approximately 36 months
Number of Days for Duration of Response for Responders	Duration of response (DOR) is defined as time from the first documented response to the date first documented disease progression or relapse or death due to any cause. For patients with solid tumors the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR.	Baseline up to approximately 36 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patient had a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative was included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
Patient had received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
Patient had progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Patients had received prior treatment with LEE011.
Patient had clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.
Patients had primary CNS tumor or CNS tumor involvement
Patient had received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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