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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02187783
First received: July 9, 2014
Last updated: September 10, 2014
Last verified: September 2014
  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: Allocation: Non-Randomized
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: August 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: Novartis Pharmaceuticals 1-855-744-6727

Locations
United States, Alaska
Alaska Clinical Research Recruiting
Anchorage, Alaska, United States, 99503
Contact    907-276-1455      
Principal Investigator: Mark Levandovsky         
United States, California
University of California Davis Cancer Center UC Davis Cancer (3) Not yet recruiting
Sacramento, California, United States, 95817
Principal Investigator: Karen Kelly         
United States, Connecticut
Yale University School of Medicine Smilow Cancer Hospital Not yet recruiting
New Haven, Connecticut, United States, 06520
Contact    +1 203 737 1906      
Principal Investigator: Joseph Paul Eder         
United States, Florida
Space Coast Medical Associates Space Coast Cancer Center Not yet recruiting
Titusville, Florida, United States, 32796
Contact    +1 855 894 4673 - ext. 3510      
Principal Investigator: Richard Levine         
United States, Georgia
Southeastern Regional Medical Center Not yet recruiting
Newnan, Georgia, United States, 30265
Contact    770-400-6629      
Principal Investigator: Navneet Dhillon         
United States, Indiana
Indiana University Indiana Univ. - Purdue Univ. Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact    317-278-8845      
Principal Investigator: Bert O'Neil         
United States, Missouri
Research Medical Center Research Med Center (2) Not yet recruiting
Kansas City, Missouri, United States, 64132
Contact    816-276-4227      
Principal Investigator: Jaswinder Singh         
United States, North Carolina
University of N.C. at Chapel Hill Physician Office Building Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Contact    919-843-5497      
Principal Investigator: Juneko Grilley-Olson         
United States, Ohio
Cleveland Clinic Taussig Cancer Institute Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact    216-444-8258      
Principal Investigator: Davendra Sohal         
United States, Oregon
Salem Health Recruiting
Salem, Oregon, United States, 97309
Contact    503-561-6455      
Principal Investigator: John Strother         
United States, South Dakota
Sanford Research Sanford Health Recruiting
Sioux Falls, South Dakota, United States, 57104
Contact    605-328-8000      
Principal Investigator: Steven Powell         
United States, Texas
Oncology Consultants Oncology Group Recruiting
Houston, Texas, United States, 77024
Contact    832-824-5383      
Principal Investigator: Julio Peguero         
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3) Not yet recruiting
Houston, Texas, United States, 77030
Contact    216-255-2748      
Principal Investigator: Vivek Subbiah         
United States, Utah
Intermountain Medical Center Intermountain Healthcare Not yet recruiting
Murray, Utah, United States, 84157
Contact    435-688-4900      
Principal Investigator: Lincoln Nadauld         
United States, Washington
Multicare Research Institute Not yet recruiting
Tacoma, Washington, United States, 98405
Contact    253-403-2554      
Principal Investigator: John A. Keech         
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: September 10, 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

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 30, 2014