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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02187783
Recruitment Status : Completed
First Posted : July 11, 2014
Results First Posted : April 16, 2019
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Tumors With CDK4/6 Pathway Activation
Intervention Drug: LEE011
Enrollment 106
Recruitment Details  
Pre-assignment Details There were 176 patients screened
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 106
Patients With Solid Tumors 105
Completed 0
Not Completed 106
Reason Not Completed
Adverse Event             8
Death             3
Progressive disease             80
Protocol Violation             3
Physician Decision             2
Withdrawal by Subject             9
Study terminated by sponsor             1
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 106
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants
60.5  (13.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
Female
56
  52.8%
Male
50
  47.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
White
90
  84.9%
Black or African American
4
   3.8%
Asian
5
   4.7%
Other
7
   6.6%
Primary tumor type   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
Adrenals
1
   0.9%
Bladder
7
   6.6%
Breast-triple negative
7
   6.6%
Cervix
1
   0.9%
Cholangio
2
   1.9%
Chordoma
1
   0.9%
Colorectal
2
   1.9%
Esophagus
3
   2.8%
Gall bladder ducts
1
   0.9%
Gastroesophageal junction
4
   3.8%
Gastrointestinal stromal tumor
1
   0.9%
Head and neck non-squamous cell carcinoma
4
   3.8%
Head and neck squamous cell carcinoma
7
   6.6%
Kidneys
2
   1.9%
Liver
2
   1.9%
Lung non-small cell adenocarcinoma
9
   8.5%
Lung non-small cell non-adenocarcinoma
2
   1.9%
Lung non-small cell squamous
6
   5.7%
Lymphoma
1
   0.9%
Mesothelioma
5
   4.7%
Neuroendocrine
2
   1.9%
Ovarian
3
   2.8%
Pancreas
5
   4.7%
Penile
1
   0.9%
Prostate
1
   0.9%
Salivary gland
1
   0.9%
Sarcoma
13
  12.3%
Skin non-melanoma
3
   2.8%
Thyroid
1
   0.9%
Unknown primary
4
   3.8%
Uterus
4
   3.8%
[1]
Measure Description: Primary tumor type was sponsor adjudicated.
Number of participants who had radiotherapy, surgery and liver metastasis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants
Prior antineoplastic radiotherapy
61
  57.5%
Prior antineoplastic surgery
92
  86.8%
Liver metastasis
29
  27.4%
Eastern Cooperative Oncology Group (ECOG) Performance Status for participants   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants
Performance status = 0 36
Performance status = 1 70
[1]
Measure Description: ECOG: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5 = Dead.
1.Primary Outcome
Title Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments
Hide Description 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
Time Frame Baseline up ≥16 weeks up to approximately 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 105
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response
0
   0.0%
Partial response (PR)
3
   2.9%
Stable disease (SD)
16
  15.2%
Progressive disease (PD)
71
  67.6%
Non-evaluable (NE)
15
  14.3%
2.Primary Outcome
Title Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS
Hide Description 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
Time Frame Baseline and ≥ 16 weeks up to approximately 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participant
19
(11.3 to 26.8)
3.Primary Outcome
Title Overall Response Rate (ORR) ≥ 16 Weeks. FAS
Hide Description ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS
Time Frame Baseline and ≥ 16 weeks up to approximately 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participant
3
(0.6 to 8.1)
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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)
Time Frame Every 8 weeks until death, assessed up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 106
Median (95% Confidence Interval)
Unit of Measure: months
1.8
(1.8 to 1.9)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame Baseline up to approximately 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 106
Median (95% Confidence Interval)
Unit of Measure: months
7.7
(5.3 to 9.2)
6.Secondary Outcome
Title Number of Days for Duration of Response for Responders
Hide Description 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.
Time Frame Baseline up to approximately 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: Days
Patient 1 254
Patient 2 330
Patient 3 985
Time Frame Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ribociclib 600 mg
Hide Arm/Group Description 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.
All-Cause Mortality
Ribociclib 600 mg
Affected / at Risk (%)
Total   14/106 (13.21%) 
Hide Serious Adverse Events
Ribociclib 600 mg
Affected / at Risk (%)
Total   40/106 (37.74%) 
Blood and lymphatic system disorders   
Anaemia  1  1/106 (0.94%) 
Febrile neutropenia  1  1/106 (0.94%) 
Thrombocytopenia  1  1/106 (0.94%) 
Cardiac disorders   
Atrial fibrillation  1  1/106 (0.94%) 
Cardio-respiratory arrest  1  1/106 (0.94%) 
Palpitations  1  1/106 (0.94%) 
Pericardial effusion  1  2/106 (1.89%) 
Gastrointestinal disorders   
Abdominal pain  1  2/106 (1.89%) 
Abdominal pain upper  1  1/106 (0.94%) 
Ascites  1  1/106 (0.94%) 
Constipation  1  1/106 (0.94%) 
Dysphagia  1  1/106 (0.94%) 
Haemorrhoids  1  1/106 (0.94%) 
Mouth haemorrhage  1  1/106 (0.94%) 
Nausea  1  3/106 (2.83%) 
Small intestinal obstruction  1  2/106 (1.89%) 
Vomiting  1  1/106 (0.94%) 
General disorders   
Asthenia  1  2/106 (1.89%) 
Non-cardiac chest pain  1  1/106 (0.94%) 
Pain  1  2/106 (1.89%) 
Infections and infestations   
Abscess  1  1/106 (0.94%) 
Peritonitis  1  1/106 (0.94%) 
Pneumonia  1  1/106 (0.94%) 
Pseudomonal sepsis  1  1/106 (0.94%) 
Pyelonephritis  1  1/106 (0.94%) 
Pyelonephritis acute  1  1/106 (0.94%) 
Sepsis  1  1/106 (0.94%) 
Urinary tract infection  1  1/106 (0.94%) 
Investigations   
Alanine aminotransferase increased  1  1/106 (0.94%) 
Aspartate aminotransferase increased  1  1/106 (0.94%) 
Blood bilirubin increased  1  1/106 (0.94%) 
Weight decreased  1  1/106 (0.94%) 
Metabolism and nutrition disorders   
Diabetic ketoacidosis  1  1/106 (0.94%) 
Failure to thrive  1  1/106 (0.94%) 
Hypomagnesaemia  1  1/106 (0.94%) 
Hyponatraemia  1  2/106 (1.89%) 
Hypophosphataemia  1  1/106 (0.94%) 
Malnutrition  1  1/106 (0.94%) 
Musculoskeletal and connective tissue disorders   
Bone pain  1  1/106 (0.94%) 
Muscular weakness  1  1/106 (0.94%) 
Pain in extremity  1  1/106 (0.94%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer pain  1  1/106 (0.94%) 
Nervous system disorders   
Aphasia  1  1/106 (0.94%) 
Embolic stroke  1  1/106 (0.94%) 
Transient ischaemic attack  1  1/106 (0.94%) 
Psychiatric disorders   
Confusional state  1  1/106 (0.94%) 
Mental status changes  1  1/106 (0.94%) 
Renal and urinary disorders   
Nephropathy toxic  1  1/106 (0.94%) 
Renal failure  1  1/106 (0.94%) 
Renal tubular necrosis  1  1/106 (0.94%) 
Ureteric obstruction  1  1/106 (0.94%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1  2/106 (1.89%) 
Dyspnoea  1  5/106 (4.72%) 
Pulmonary embolism  1  1/106 (0.94%) 
Respiratory failure  1  2/106 (1.89%) 
Vascular disorders   
Deep vein thrombosis  1  1/106 (0.94%) 
Hypotension  1  1/106 (0.94%) 
Thrombophlebitis superficial  1  1/106 (0.94%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ribociclib 600 mg
Affected / at Risk (%)
Total   104/106 (98.11%) 
Blood and lymphatic system disorders   
Anaemia  1  26/106 (24.53%) 
Leukopenia  1  12/106 (11.32%) 
Neutropenia  1  33/106 (31.13%) 
Thrombocytopenia  1  13/106 (12.26%) 
Gastrointestinal disorders   
Abdominal pain  1  10/106 (9.43%) 
Constipation  1  21/106 (19.81%) 
Diarrhoea  1  28/106 (26.42%) 
Dyspepsia  1  8/106 (7.55%) 
Nausea  1  46/106 (43.40%) 
Vomiting  1  31/106 (29.25%) 
General disorders   
Asthenia  1  8/106 (7.55%) 
Chest pain  1  8/106 (7.55%) 
Fatigue  1  45/106 (42.45%) 
Oedema peripheral  1  12/106 (11.32%) 
Pyrexia  1  8/106 (7.55%) 
Infections and infestations   
Urinary tract infection  1  11/106 (10.38%) 
Investigations   
Alanine aminotransferase increased  1  11/106 (10.38%) 
Aspartate aminotransferase increased  1  11/106 (10.38%) 
Blood alkaline phosphatase increased  1  8/106 (7.55%) 
Blood creatinine increased  1  15/106 (14.15%) 
Electrocardiogram QT prolonged  1  12/106 (11.32%) 
Gamma-glutamyltransferase increased  1  9/106 (8.49%) 
Lymphocyte count decreased  1  8/106 (7.55%) 
Neutrophil count decreased  1  16/106 (15.09%) 
Platelet count decreased  1  9/106 (8.49%) 
Weight decreased  1  9/106 (8.49%) 
White blood cell count decreased  1  19/106 (17.92%) 
Metabolism and nutrition disorders   
Decreased appetite  1  21/106 (19.81%) 
Dehydration  1  7/106 (6.60%) 
Hyperglycaemia  1  9/106 (8.49%) 
Hypoalbuminaemia  1  7/106 (6.60%) 
Hypokalaemia  1  7/106 (6.60%) 
Hypomagnesaemia  1  9/106 (8.49%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  8/106 (7.55%) 
Back pain  1  12/106 (11.32%) 
Muscular weakness  1  7/106 (6.60%) 
Musculoskeletal pain  1  8/106 (7.55%) 
Myalgia  1  6/106 (5.66%) 
Pain in extremity  1  7/106 (6.60%) 
Nervous system disorders   
Dizziness  1  13/106 (12.26%) 
Headache  1  9/106 (8.49%) 
Psychiatric disorders   
Anxiety  1  7/106 (6.60%) 
Confusional state  1  6/106 (5.66%) 
Insomnia  1  11/106 (10.38%) 
Renal and urinary disorders   
Proteinuria  1  6/106 (5.66%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  15/106 (14.15%) 
Dyspnoea  1  20/106 (18.87%) 
Epistaxis  1  6/106 (5.66%) 
Oropharyngeal pain  1  6/106 (5.66%) 
Skin and subcutaneous tissue disorders   
Rash  1  6/106 (5.66%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 1-888-669-6682
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02187783    
Other Study ID Numbers: CLEE011XUS03
First Submitted: July 9, 2014
First Posted: July 11, 2014
Results First Submitted: January 16, 2019
Results First Posted: April 16, 2019
Last Update Posted: July 18, 2019