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

NCT02187783 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CLEE011XUS03
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 61

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.

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments

  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

  Baseline up ≥16 weeks up to approximately 36 months

• Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS

  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

  Baseline and ≥ 16 weeks up to approximately 36 months

• Overall Response Rate (ORR) ≥ 16 Weeks. FAS

  ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS

  Baseline and ≥ 16 weeks up to approximately 36 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Every 8 weeks until death, assessed up to 24 months

• Overall Survival (OS)

  Baseline up to approximately 36 months

• Number of Days for Duration of Response for Responders

  Baseline up to approximately 36 months

Study Arms (1)

LEE011

EXPERIMENTAL

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.

Drug: LEE011

Interventions

LEE011 DRUG

Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally

LEE011

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (61)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Alaska Clinical Research

Anchorage, Alaska, 99503, United States

Location

Arizona Oncology Associates Dept. Of Onc.

Phoenix, Arizona, United States

Location

University of Arkansas/ Arkansas Cancer Research Center UA Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

PCR Oncology

Pismo Beach, California, 93449, United States

Location

University of California Davis Cancer Center UC Davis Cancer (3)

Sacramento, California, 95817, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Danbury Hospital

Danbury, Connecticut, 06810, United States

Location

Yale University School of Medicine Smilow Cancer Hospital

New Haven, Connecticut, 06520, United States

Location

Whittingham Cancer Center Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Stamford Hospital Med. Oncology Hematology Res.

Stamford, Connecticut, 06902, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

NorthWest Georgia Oncology Centers NW Georgia Oncology

Marietta, Georgia, 30060, United States

Location

Harbin Clinic Medical Oncology Clin. Res.

Rome, Georgia, 30165, United States

Location

Queen's Medical Center Queens Cancer Center

Honolulu, Hawaii, 96817, United States

Location

Northwestern Medicine Developmental Therapeutics Institute

Chicago, Illinois, 60611, United States

Location

Indiana University Indiana Univ. - Purdue Univ.

Indianapolis, Indiana, 46202, United States

Location

Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.

South Bend, Indiana, 46617, United States

Location

University of Iowa Hospitals & Clinics Regulatory Contact 2

Iowa City, Iowa, 52242, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

St. Agnes Hospital St. Agnes Hospital (2)

Baltimore, Maryland, 21229, United States

Location

Michigan Medicine University of Michigan Int. Medicine Oncology

Ann Arbor, Michigan, 48109 5271, United States

Location

Cancer and Hematology Centers of West Michigan Dept. of Oncology

Grand Rapids, Michigan, 49546, United States

Location

Saint Luke's Hospital/Marion Bloch Neuroscience Institute St. Luke's Hospital (4)

Kansas City, Missouri, 64111, United States

Location

Research Medical Center Research Med Center (2)

Kansas City, Missouri, 64132, United States

Location

Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)

Las Vegas, Nevada, 89109, United States

Location

Cooper Health System Cooper Health System (5)

Camden, New Jersey, 08103, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Cancer Center at Presbyterian

Albuquerque, New Mexico, United States

Location

Broome Oncology Broome Oncology (2)

Johnson City, New York, 13790, United States

Location

University of N C at Chapel Hill Physician Office Building

Chapel Hill, North Carolina, 27599-7600, United States

Location

Carolina Oncology Specialists, PC

Hickory, North Carolina, 28602, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Oncology Hematology Care Inc Oncology Hematology Care 2

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center Comprehensive Cancer Center

Columbus, Ohio, 43221, United States

Location

Oregon Health and Science University Oregon Health & Science U (56)

Portland, Oregon, 97239, United States

Location

Salem Health

Salem, Oregon, 97309, United States

Location

Fox Chase Cancer Center Dept of Medical Oncology

Philadelphia, Pennsylvania, 19111, United States

Location

Rhode Island Hospital Rhode Island Hosp. (2)

Providence, Rhode Island, 02903, United States

Location

Greenville Health System ITOR - Cancer Institute

Greenville, South Carolina, 29615, United States

Location

Sanford University of South Dakota Medical Center Sanford Health

Sioux Falls, South Dakota, 57104, United States

Location

Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology

Chattanooga, Tennessee, 37404, United States

Location

The West Clinic Dept. of the West Clinic

Memphis, Tennessee, 38120, United States

Location

Tennessee Oncology Tennessee Oncology (3)

Nashville, Tennessee, 37203, United States

Location

Coastal Bend Cancer Center

Corpus Christi, Texas, 78404, United States

Location

Oncology Consultants Oncology Group

Houston, Texas, 77024, United States

Location

MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio Cancer Therapy & Research Ctr.

San Antonio, Texas, 78229, United States

Location

Intermountain Medical Center Intermountain Healthcare

Murray, Utah, 84157, United States

Location

Utah Cancer Specialists Utah Cancer Specialists (11)

Salt Lake City, Utah, 84106, United States

Location

Shenandoah Oncology Shenadoah Oncology (2)

Winchester, Virginia, 22601, United States

Location

Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc

Kennewick, Washington, 99336, United States

Location

Vista Oncology Inc. PS

Olympia, Washington, 98502, United States

Location

Multicare Research Institute

Tacoma, Washington, 98405, United States

Location

Northwest Medical Specialties Rainier Physicians, PC

Tacoma, Washington, 98405, United States

Location

Providence St. Mary Regional Cancer Center

Walla Walla, Washington, 98057, United States

Location

Wenatchee Valley Medical Center Wenatchee Valley

Wenatchee, Washington, 98801, United States

Location

Aurora Research Institute Aurora Health Care

Milwaukee, Wisconsin, 53226, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Lymphoma; Mesothelioma; Leukemia; Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

1-888-669-6682

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2014
• First Posted: July 11, 2014
• Study Start: August 25, 2014
• Primary Completion: January 17, 2018
• Study Completion: January 17, 2018
• Last Updated: July 18, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-07

Locations

US (61)