Tumors With CDK4/6 Pathway ActivationPhase 2SIGNATURENCT02187783
LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)
A Phase 2 study testing LEE011 in people with Tumors With CDK4/6 Pathway Activation, run by Novartis Pharmaceuticals at 61 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumors With CDK4/6 Pathway Activation
- What is being tested?
- LEE011
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 61 sitesUnited States
- Study dates
- 25 Aug 2014to 17 Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
61 sites in 1 country.
61 sites in 1 country
United States61 sites
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, 87106
Cancer Center at Presbyterian
Albuquerque, New Mexico
Alaska Clinical Research
Anchorage, Alaska, 99503
Michigan Medicine University of Michigan Int. Medicine Oncology
Ann Arbor, Michigan, 48109 5271
St. Agnes Hospital St. Agnes Hospital (2)
Baltimore, Maryland, 21229
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Cooper Health System Cooper Health System (5)
Camden, New Jersey, 08103
University of N C at Chapel Hill Physician Office Building
Chapel Hill, North Carolina, 27599-7600
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
Chattanooga, Tennessee, 37404
Northwestern Medicine Developmental Therapeutics Institute
Chicago, Illinois, 60611
Oncology Hematology Care Inc Oncology Hematology Care 2
Cincinnati, Ohio, 45242
Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, 44195
Ohio State University Medical Center Comprehensive Cancer Center
Columbus, Ohio, 43221
Coastal Bend Cancer Center
Corpus Christi, Texas, 78404
Danbury Hospital
Danbury, Connecticut, 06810
Sarah Cannon Research Institute
Denver, Colorado, 80218
Cancer and Hematology Centers of West Michigan Dept. of Oncology
Grand Rapids, Michigan, 49546
Greenville Health System ITOR - Cancer Institute
Greenville, South Carolina, 29615
Carolina Oncology Specialists, PC
Hickory, North Carolina, 28602
Queen's Medical Center Queens Cancer Center
Honolulu, Hawaii, 96817
Oncology Consultants Oncology Group
Houston, Texas, 77024
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
Houston, Texas, 77030
Indiana University Indiana Univ. - Purdue Univ.
Indianapolis, Indiana, 46202
University of Iowa Hospitals & Clinics Regulatory Contact 2
Iowa City, Iowa, 52242
Broome Oncology Broome Oncology (2)
Johnson City, New York, 13790
Saint Luke's Hospital/Marion Bloch Neuroscience Institute St. Luke's Hospital (4)
Kansas City, Missouri, 64111
Research Medical Center Research Med Center (2)
Kansas City, Missouri, 64132
Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
Kennewick, Washington, 99336
Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
Las Vegas, Nevada, 89109
University of Arkansas/ Arkansas Cancer Research Center UA Medical Sciences
Little Rock, Arkansas, 72205
NorthWest Georgia Oncology Centers NW Georgia Oncology
Marietta, Georgia, 30060
The West Clinic Dept. of the West Clinic
Memphis, Tennessee, 38120
Aurora Research Institute Aurora Health Care
Milwaukee, Wisconsin, 53226
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
Intermountain Medical Center Intermountain Healthcare
Murray, Utah, 84157
Tennessee Oncology Tennessee Oncology (3)
Nashville, Tennessee, 37203
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Yale University School of Medicine Smilow Cancer Hospital
New Haven, Connecticut, 06520
Whittingham Cancer Center Norwalk Hospital
Norwalk, Connecticut, 06856
Vista Oncology Inc. PS
Olympia, Washington, 98502
Florida Hospital Cancer Institute
Orlando, Florida, 32804
Fox Chase Cancer Center Dept of Medical Oncology
Philadelphia, Pennsylvania, 19111
Arizona Oncology Associates Dept. Of Onc.
Phoenix, Arizona
PCR Oncology
Pismo Beach, California, 93449
Oregon Health and Science University Oregon Health & Science U (56)
Portland, Oregon, 97239
Rhode Island Hospital Rhode Island Hosp. (2)
Providence, Rhode Island, 02903
Harbin Clinic Medical Oncology Clin. Res.
Rome, Georgia, 30165
University of California Davis Cancer Center UC Davis Cancer (3)
Sacramento, California, 95817
Salem Health
Salem, Oregon, 97309
Utah Cancer Specialists Utah Cancer Specialists (11)
Salt Lake City, Utah, 84106
University of Texas Health Science Center at San Antonio Cancer Therapy & Research Ctr.
San Antonio, Texas, 78229
New England Cancer Specialists
Scarborough, Maine, 04074
Sanford University of South Dakota Medical Center Sanford Health
Sioux Falls, South Dakota, 57104
Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.
South Bend, Indiana, 46617
Stamford Hospital Med. Oncology Hematology Res.
Stamford, Connecticut, 06902
Multicare Research Institute
Tacoma, Washington, 98405
Northwest Medical Specialties Rainier Physicians, PC
Tacoma, Washington, 98405
Providence St. Mary Regional Cancer Center
Walla Walla, Washington, 98057
Wenatchee Valley Medical Center Wenatchee Valley
Wenatchee, Washington, 98801
Shenandoah Oncology Shenadoah Oncology (2)
Winchester, Virginia, 22601
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
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
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
- Being tested
- LEE011
- 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
- Medical subject headings
- Hematologic Neoplasms, Breast Neoplasms, Ovarian Neoplasms, Lymphoma, Mesothelioma, Leukemia, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEE011Drug
Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: LEE011 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: Baseline and ≥ 16 weeks up to approximately 36 months
Secondary outcomes (3)
Progression Free Survival (PFS)
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)
Measured: Every 8 weeks until death, assessed up to 24 months
Overall Survival (OS)
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.
Measured: Baseline up to approximately 36 months
Number of Days for Duration of Response for Responders
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.
Measured: Baseline up to approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2014 (estimated)
- Study start25 Aug 2014
- Primary completion17 Jan 2018
- Study completion17 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tumors With CDK4/6 Pathway ActivationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02187783
- Sponsor's protocol ID
- CLEE011XUS03
- Acronym
- SIGNATURE
- Status last verified
- Jul 2019
- First submitted
- 9 Jul 2014
- Last updated
- 18 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02187783
- Acronym / sponsor ID
- SIGNATURE / CLEE011XUS03
- Conditions
- Tumors With CDK4/6 Pathway Activation
- Keywords
- Solid malignancy, Hematologic malignancy, Mutations, Amplifications, Signature, CDK4, CDK6, CDK4/6
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Aug 2014 (actual)
- Primary completion
- 17 Jan 2018 (actual)
- Study completion
- 17 Jan 2018 (actual)
- First posted
- 11 Jul 2014 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LEE011 | Experimental | Drug: LEE011LEE011 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LEE011Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally | Drug | LEE011 |
Primary outcome
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
Time frame: 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
Time frame: 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
Time frame: 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
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: Every 8 weeks until death, assessed up to 24 months
Overall Survival (OS)
Time frame: Baseline up to approximately 36 months
Number of Days for Duration of Response for Responders
Time frame: Baseline up to approximately 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
61 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LEE011 in people with Tumors With CDK4/6 Pathway Activation, run by Novartis Pharmaceuticals at 61 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments (time frame: Baseline up ≥16 weeks up to approximately 36 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2019.