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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02187783
First received: July 9, 2014
Last updated: NA
Last verified: July 2014
History: No changes posted
  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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Clinical benefit rate associated with LEE011 treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 90
Study Start Date: July 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LEE011
Adult 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.
Drug: LEE011
LEE011 600 mg (hard gelatin capsules) will be administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle is defined as 28 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02187783

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Enrollment Call Center 1-855-744-6727

Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02187783     History of Changes
Other Study ID Numbers: CLEE011XUS03
Study First Received: July 9, 2014
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 23, 2014