LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)
- Registration Number
- NCT02187783
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 106
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LEE011 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments 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
Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS 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
Overall Response Rate (ORR) ≥ 16 Weeks. FAS 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
Name Time Method Progression Free Survival (PFS) 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)
Overall Survival (OS) 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.
Number of Days for Duration of Response for Responders 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.
Trial Locations
- Locations (61)
Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.
🇺🇸South Bend, Indiana, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
PCR Oncology
🇺🇸Pismo Beach, California, United States
Alaska Clinical Research
🇺🇸Anchorage, Alaska, United States
Whittingham Cancer Center Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Broome Oncology Broome Oncology (2)
🇺🇸Johnson City, New York, United States
Carolina Oncology Specialists, PC
🇺🇸Hickory, North Carolina, United States
Salem Health
🇺🇸Salem, Oregon, United States
St. Agnes Hospital St. Agnes Hospital (2)
🇺🇸Baltimore, Maryland, United States
Northwestern Medicine Developmental Therapeutics Institute
🇺🇸Chicago, Illinois, United States
Indiana University Indiana Univ. - Purdue Univ.
🇺🇸Indianapolis, Indiana, United States
Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
🇺🇸Las Vegas, Nevada, United States
Oncology Consultants Oncology Group
🇺🇸Houston, Texas, United States
Oncology Hematology Care Inc Oncology Hematology Care 2
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Foundation Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio Cancer Therapy & Research Ctr.
🇺🇸San Antonio, Texas, United States
Tennessee Oncology Tennessee Oncology (3)
🇺🇸Nashville, Tennessee, United States
Utah Cancer Specialists Utah Cancer Specialists (11)
🇺🇸Salt Lake City, Utah, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Oncology Associates Dept. Of Onc.
🇺🇸Phoenix, Arizona, United States
Yale University School of Medicine Smilow Cancer Hospital
🇺🇸New Haven, Connecticut, United States
Sarah Cannon Research Institute
🇺🇸Denver, Colorado, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
Queen's Medical Center Queens Cancer Center
🇺🇸Honolulu, Hawaii, United States
Harbin Clinic Medical Oncology Clin. Res.
🇺🇸Rome, Georgia, United States
University of Iowa Hospitals & Clinics Regulatory Contact 2
🇺🇸Iowa City, Iowa, United States
New Mexico Cancer Care Alliance
🇺🇸Albuquerque, New Mexico, United States
Saint Luke's Hospital/Marion Bloch Neuroscience Institute St. Luke's Hospital (4)
🇺🇸Kansas City, Missouri, United States
Research Medical Center Research Med Center (2)
🇺🇸Kansas City, Missouri, United States
Cancer Center at Presbyterian
🇺🇸Albuquerque, New Mexico, United States
University of N C at Chapel Hill Physician Office Building
🇺🇸Chapel Hill, North Carolina, United States
Oregon Health and Science University Oregon Health & Science U (56)
🇺🇸Portland, Oregon, United States
Fox Chase Cancer Center Dept of Medical Oncology
🇺🇸Philadelphia, Pennsylvania, United States
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
🇺🇸Chattanooga, Tennessee, United States
Coastal Bend Cancer Center
🇺🇸Corpus Christi, Texas, United States
The West Clinic Dept. of the West Clinic
🇺🇸Memphis, Tennessee, United States
Intermountain Medical Center Intermountain Healthcare
🇺🇸Murray, Utah, United States
Aurora Research Institute Aurora Health Care
🇺🇸Milwaukee, Wisconsin, United States
Multicare Research Institute
🇺🇸Tacoma, Washington, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Stamford Hospital Med. Oncology Hematology Res.
🇺🇸Stamford, Connecticut, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Ohio State University Medical Center Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Arkansas/ Arkansas Cancer Research Center UA Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Michigan Medicine University of Michigan Int. Medicine Oncology
🇺🇸Ann Arbor, Michigan, United States
Danbury Hospital
🇺🇸Danbury, Connecticut, United States
NorthWest Georgia Oncology Centers NW Georgia Oncology
🇺🇸Marietta, Georgia, United States
University of California Davis Cancer Center UC Davis Cancer (3)
🇺🇸Sacramento, California, United States
Cooper Health System Cooper Health System (5)
🇺🇸Camden, New Jersey, United States
Rhode Island Hospital Rhode Island Hosp. (2)
🇺🇸Providence, Rhode Island, United States
Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
🇺🇸Kennewick, Washington, United States
Cancer and Hematology Centers of West Michigan Dept. of Oncology
🇺🇸Grand Rapids, Michigan, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Sanford University of South Dakota Medical Center Sanford Health
🇺🇸Sioux Falls, South Dakota, United States
Greenville Health System ITOR - Cancer Institute
🇺🇸Greenville, South Carolina, United States
Shenandoah Oncology Shenadoah Oncology (2)
🇺🇸Winchester, Virginia, United States
Vista Oncology Inc. PS
🇺🇸Olympia, Washington, United States
Northwest Medical Specialties Rainier Physicians, PC
🇺🇸Tacoma, Washington, United States
Providence St. Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
Wenatchee Valley Medical Center Wenatchee Valley
🇺🇸Wenatchee, Washington, United States
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