Clinical Trials /

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

NCT02187783

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Cancer
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CLEE011XUS03
  • NCT ID: NCT02187783

Conditions

  • Tumors With CDK4/6 Pathway Activation

Interventions

DrugSynonymsArms
LEE011LEE011

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
LEE011ExperimentalAdult patients with a diagnosis of a solid tumor or hematological malignancy that have been pre-identified as having relevant CDK4/6, cyclin D1/3, or p16 aberrations. Patients must have received at least one prior treatment for their recurrent, metastatic and/or locally advanced disease and have no remaining standard therapy options anticipated to result in a durable response.
  • LEE011

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has a confirmed diagnosis of a select solid tumor (except breast cancer
             (however, triple negative will be 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 has 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 has progressive and measurable disease as per RECIST 1.1. or other appropriate
             hematological guidelines.

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

        Exclusion Criteria:

          -  Patients has received prior treatment with LEE011.

          -  Patient has 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 has primary CNS tumor or CNS tumor involvement

          -  Patient has received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting
             study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical benefit rate associated with LEE011 treatment
Time Frame:16 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS)
Time Frame:Every 8 weeks until death, assessed up to 24 months
Safety Issue:
Description: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
Measure:Overall Survival (OS)
Time Frame:Every 8 weeks until death, assessed up to 36 months
Safety Issue:
Description:Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.
Measure:Duration of Response (DOR)
Time Frame:Baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months
Safety Issue:
Description: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.
Measure:Safety and tolerability
Time Frame:Baseline up to 30 days after last study treatment
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Solid malignancy,
  • Hematologic malignancy,
  • Mutations,
  • Amplifications,
  • Signature,
  • CDK4,
  • CDK6,
  • CDK4/6,
  • Cyclin D1,
  • CCND1,
  • Cyclin D3,
  • CCND3,
  • p16 mutation,
  • CDKN2A,
  • LEE011,
  • Breast cancer,
  • Ovarian cancer,
  • Lymphoma,
  • Mesothelioma,
  • Pancreatic neuroendocrine,
  • Leukemia
  • Tumor

Last Updated

October 24, 2017