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

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ClinicalTrials.gov Identifier: NCT02187783
Recruitment Status : Completed
First Posted : July 11, 2014
Results First Posted : April 16, 2019
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE July 9, 2014
First Posted Date  ICMJE July 11, 2014
Results First Submitted Date  ICMJE January 16, 2019
Results First Posted Date  ICMJE April 16, 2019
Last Update Posted Date July 18, 2019
Actual Study Start Date  ICMJE August 25, 2014
Actual Primary Completion Date January 17, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 9, 2014)
Clinical benefit rate associated with LEE011 treatment [ Time Frame: 16 weeks ]
Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria will apply.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • 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)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2014)
  • Overall Response (OR) of Partial Response (PR) or greater [ Time Frame: Baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ]
    Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply.
  • Progression Free Survival (PFS) [ Time Frame: Every 8 weeks until death, assessed up to 24 months ]
    Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause
  • Overall Survival (OS) [ Time Frame: Every 8 weeks until death, assessed up to 36 months ]
    Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.
  • Duration of Response (DOR) [ Time Frame: Baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 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.
  • Safety and tolerability [ Time Frame: Baseline up to 30 days after last study treatment ]
    Safety and tolerability will be based on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g., electrocardiogram, vital signs) will be considered as appropriate.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tumors With CDK4/6 Pathway Activation
Intervention  ICMJE Drug: LEE011
Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally
Study Arms  ICMJE 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.
Intervention: Drug: LEE011
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 8, 2016)
106
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2014)
90
Actual Study Completion Date  ICMJE January 17, 2018
Actual Primary Completion Date January 17, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02187783
Other Study ID Numbers  ICMJE CLEE011XUS03
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP