Clinical trial NCT02187783: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tumors With CDK4/6 Pathway Activation
Keywords: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-07-11
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
timeFrame: Baseline up ≥16 weeks up to approximately 36 months
measure: Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS
timeFrame: Baseline and ≥ 16 weeks up to approximately 36 months
measure: Overall Response Rate (ORR) ≥ 16 Weeks. FAS
timeFrame: Baseline and ≥ 16 weeks up to approximately 36 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Every 8 weeks until death, assessed up to 24 months
measure: Overall Survival (OS)
timeFrame: Baseline up to approximately 36 months
measure: Number of Days for Duration of Response for Responders
timeFrame: Baseline up to approximately 36 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Anchorage
country: United States
facility: Alaska Clinical Research
state: Alaska
city: Phoenix
country: United States
facility: Arizona Oncology Associates Dept. Of Onc.
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas/ Arkansas Cancer Research Center UA Medical Sciences
state: Arkansas
city: Pismo Beach
country: United States
facility: PCR Oncology
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center UC Davis Cancer (3)
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine Smilow Cancer Hospital
state: Connecticut
city: Norwalk
country: United States
facility: Whittingham Cancer Center Norwalk Hospital
state: Connecticut
city: Stamford
country: United States
facility: Stamford Hospital Med. Oncology Hematology Res.
state: Connecticut
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Marietta
country: United States
facility: NorthWest Georgia Oncology Centers NW Georgia Oncology
state: Georgia
city: Rome
country: United States
facility: Harbin Clinic Medical Oncology Clin. Res.
state: Georgia
city: Honolulu
country: United States
facility: Queen's Medical Center Queens Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Medicine Developmental Therapeutics Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Indiana Univ. - Purdue Univ.
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics Regulatory Contact 2
state: Iowa
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Baltimore
country: United States
facility: St. Agnes Hospital St. Agnes Hospital (2)
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Medicine University of Michigan Int. Medicine Oncology
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of West Michigan Dept. of Oncology
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital/Marion Bloch Neuroscience Institute St. Luke's Hospital (4)
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center Research Med Center (2)
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
state: Nevada
city: Camden
country: United States
facility: Cooper Health System Cooper Health System (5)
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Albuquerque
country: United States
facility: Cancer Center at Presbyterian
state: New Mexico
city: Johnson City
country: United States
facility: Broome Oncology Broome Oncology (2)
state: New York
city: Chapel Hill
country: United States
facility: University of N C at Chapel Hill Physician Office Building
state: North Carolina
city: Hickory
country: United States
facility: Carolina Oncology Specialists, PC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc Oncology Hematology Care 2
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation Taussig Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Oregon Health & Science U (56)
state: Oregon
city: Salem
country: United States
facility: Salem Health
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center Dept of Medical Oncology
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital Rhode Island Hosp. (2)
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Health System ITOR - Cancer Institute
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford University of South Dakota Medical Center Sanford Health
state: South Dakota
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic Dept. of the West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Tennessee Oncology (3)
state: Tennessee
city: Corpus Christi
country: United States
facility: Coastal Bend Cancer Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants Oncology Group
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio Cancer Therapy & Research Ctr.
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center Intermountain Healthcare
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Utah Cancer Specialists (11)
state: Utah
city: Winchester
country: United States
facility: Shenandoah Oncology Shenadoah Oncology (2)
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
state: Washington
city: Olympia
country: United States
facility: Vista Oncology Inc. PS
state: Washington
city: Tacoma
country: United States
facility: Multicare Research Institute
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties Rainier Physicians, PC
state: Washington
city: Walla Walla
country: United States
facility: Providence St. Mary Regional Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center Wenatchee Valley
state: Washington
city: Milwaukee
country: United States
facility: Aurora Research Institute Aurora Health Care
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
References: