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

July 16, 2019 updated by: Novartis Pharmaceuticals

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 8 - LEE011 for Patients With CDK4/6 Pathway Activated Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
106

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

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

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • University of Alabama at Birmingham
    • Alaska
      • Anchorage, Alaska, United States, 99503
        • Alaska Clinical Research
    • Arizona
      • Phoenix, Arizona, United States
        • Arizona Oncology Associates Dept. Of Onc.
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas/ Arkansas Cancer Research Center UA Medical Sciences
    • California
      • Pismo Beach, California, United States, 93449
        • PCR Oncology
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center UC Davis Cancer (3)
    • Colorado
      • Denver, Colorado, United States, 80218
        • Sarah Cannon Research Institute
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Danbury Hospital
      • New Haven, Connecticut, United States, 06520
        • Yale University School Of Medicine Smilow Cancer Hospital
      • Norwalk, Connecticut, United States, 06856
        • Whittingham Cancer Center Norwalk Hospital
      • Stamford, Connecticut, United States, 06902
        • Stamford Hospital Med. Oncology Hematology Res.
    • Florida
      • Orlando, Florida, United States, 32804
        • Florida Hospital Cancer Institute
    • Georgia
      • Marietta, Georgia, United States, 30060
        • NorthWest Georgia Oncology Centers NW Georgia Oncology
      • Rome, Georgia, United States, 30165
        • Harbin Clinic Medical Oncology Clin. Res.
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Queen's Medical Center Queens Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Medicine Developmental Therapeutics Institute
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Indiana Univ. - Purdue Univ.
      • South Bend, Indiana, United States, 46617
        • Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals & Clinics Regulatory Contact 2
    • Maine
      • Scarborough, Maine, United States, 04074
        • New England Cancer Specialists
    • Maryland
      • Baltimore, Maryland, United States, 21229
        • St. Agnes Hospital St. Agnes Hospital (2)
    • Michigan
      • Ann Arbor, Michigan, United States, 48109 5271
        • Michigan Medicine University of Michigan Int. Medicine Oncology
      • Grand Rapids, Michigan, United States, 49546
        • Cancer and Hematology Centers of West Michigan Dept. of Oncology
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital/Marion Bloch Neuroscience Institute St. Luke's Hospital (4)
      • Kansas City, Missouri, United States, 64132
        • Research Medical Center Research Med Center (2)
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper Health System Cooper Health System (5)
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • New Mexico Cancer Care Alliance
      • Albuquerque, New Mexico, United States
        • Cancer Center at Presbyterian
    • New York
      • Johnson City, New York, United States, 13790
        • Broome Oncology Broome Oncology (2)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7600
        • University of N C at Chapel Hill Physician Office Building
      • Hickory, North Carolina, United States, 28602
        • Carolina Oncology Specialists, PC
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Baptist Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care Inc Oncology Hematology Care 2
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation Taussig Cancer Institute
      • Columbus, Ohio, United States, 43221
        • Ohio State University Medical Center Comprehensive Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University Oregon Health & Science U (56)
      • Salem, Oregon, United States, 97309
        • SALEM Health
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center Dept of Medical Oncology
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital Rhode Island Hosp. (2)
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • Greenville Health System ITOR - Cancer Institute
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford University of South Dakota Medical Center Sanford Health
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
      • Memphis, Tennessee, United States, 38120
        • The West Clinic Dept. of the West Clinic
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology Tennessee Oncology (3)
    • Texas
      • Corpus Christi, Texas, United States, 78404
        • Coastal Bend Cancer Center
      • Houston, Texas, United States, 77024
        • Oncology Consultants Oncology Group
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio Cancer Therapy & Research Ctr.
    • Utah
      • Murray, Utah, United States, 84157
        • Intermountain Medical Center Intermountain Healthcare
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists Utah Cancer Specialists (11)
    • Virginia
      • Winchester, Virginia, United States, 22601
        • Shenandoah Oncology Shenadoah Oncology (2)
    • Washington
      • Kennewick, Washington, United States, 99336
        • Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
      • Olympia, Washington, United States, 98502
        • Vista Oncology Inc. PS
      • Tacoma, Washington, United States, 98405
        • MultiCare Research Institute
      • Tacoma, Washington, United States, 98405
        • Northwest Medical Specialties Rainier Physicians, PC
      • Walla Walla, Washington, United States, 98057
        • Providence St. Mary Regional Cancer Center
      • Wenatchee, Washington, United States, 98801
        • Wenatchee Valley Medical Center Wenatchee Valley
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin Cancer Center
      • Milwaukee, Wisconsin, United States, 53226
        • Aurora Research Institute Aurora Health Care

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

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

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
Time Frame: Baseline up ≥16 weeks up to approximately 36 months
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
Time Frame: Baseline and ≥ 16 weeks up to approximately 36 months
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
Time Frame: Baseline and ≥ 16 weeks up to approximately 36 months
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Every 8 weeks until death, assessed up to 24 months
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)
Time Frame: Baseline up to approximately 36 months
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
Time Frame: Baseline up to approximately 36 months
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

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 25, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 17, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 17, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 9, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 11, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLEE011XUS03

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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