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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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 )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Tumors With CDK4/6 Pathway Activation Drug: LEE011 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 25, 2014
Actual Primary Completion Date : January 17, 2018
Actual Study Completion Date : January 17, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ribociclib

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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)

  2. 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.

  3. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02187783


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] September 27, 2015
Study Protocol  [PDF] April 10, 2017

More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02187783    
Other Study ID Numbers: CLEE011XUS03
First Posted: July 11, 2014    Key Record Dates
Results First Posted: April 16, 2019
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Solid malignancy
Hematologic malignancy
Mutations
Amplifications
Signature
CDK4
CDK6
CDK4/6
Cyclin D1
CCND,
Cyclin D3
 p16 mutation
CDKN2A
LEE011
Breast cancer
Ovarian cancer
Lymphoma
Mesothelioma
Pancreatic neuroendocrine
Leukemia
Tumor
Additional relevant MeSH terms:
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Neoplasms