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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02187783
• Collaborator: (none)
• Enrollment: 106
• Locations: 61
• Arm: 1
• Actual Duration (Months): 40.8
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tumors With CDK4/6 Pathway Activation	Drug: LEE011	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 25, 2014
• Actual Primary Completion Date: Jan 17, 2018
• Actual Study Completion Date: Jan 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: LEE011; Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. 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

1. 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)

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	Alaska Clinical Research	Anchorage	Alaska	United States	99503
3	Arizona Oncology Associates Dept. Of Onc.	Phoenix	Arizona	United States
4	University of Arkansas/ Arkansas Cancer Research Center UA Medical Sciences	Little Rock	Arkansas	United States	72205
5	PCR Oncology	Pismo Beach	California	United States	93449
6	University of California Davis Cancer Center UC Davis Cancer (3)	Sacramento	California	United States	95817
7	Sarah Cannon Research Institute	Denver	Colorado	United States	80218
8	Danbury Hospital	Danbury	Connecticut	United States	06810
9	Yale University School of Medicine Smilow Cancer Hospital	New Haven	Connecticut	United States	06520
10	Whittingham Cancer Center Norwalk Hospital	Norwalk	Connecticut	United States	06856
11	Stamford Hospital Med. Oncology Hematology Res.	Stamford	Connecticut	United States	06902
12	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
13	NorthWest Georgia Oncology Centers NW Georgia Oncology	Marietta	Georgia	United States	30060
14	Harbin Clinic Medical Oncology Clin. Res.	Rome	Georgia	United States	30165
15	Queen's Medical Center Queens Cancer Center	Honolulu	Hawaii	United States	96817
16	Northwestern Medicine Developmental Therapeutics Institute	Chicago	Illinois	United States	60611
17	Indiana University Indiana Univ. - Purdue Univ.	Indianapolis	Indiana	United States	46202
18	Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.	South Bend	Indiana	United States	46617
19	University of Iowa Hospitals & Clinics Regulatory Contact 2	Iowa City	Iowa	United States	52242
20	New England Cancer Specialists	Scarborough	Maine	United States	04074
21	St. Agnes Hospital St. Agnes Hospital (2)	Baltimore	Maryland	United States	21229
22	Michigan Medicine University of Michigan Int. Medicine Oncology	Ann Arbor	Michigan	United States	48109 5271
23	Cancer and Hematology Centers of West Michigan Dept. of Oncology	Grand Rapids	Michigan	United States	49546
24	Saint Luke's Hospital/Marion Bloch Neuroscience Institute St. Luke's Hospital (4)	Kansas City	Missouri	United States	64111
25	Research Medical Center Research Med Center (2)	Kansas City	Missouri	United States	64132
26	Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)	Las Vegas	Nevada	United States	89109
27	Cooper Health System Cooper Health System (5)	Camden	New Jersey	United States	08103
28	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
29	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87106
30	Cancer Center at Presbyterian	Albuquerque	New Mexico	United States
31	Broome Oncology Broome Oncology (2)	Johnson City	New York	United States	13790
32	University of N C at Chapel Hill Physician Office Building	Chapel Hill	North Carolina	United States	27599-7600
33	Carolina Oncology Specialists, PC	Hickory	North Carolina	United States	28602
34	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
35	Oncology Hematology Care Inc Oncology Hematology Care 2	Cincinnati	Ohio	United States	45242
36	Cleveland Clinic Foundation Taussig Cancer Institute	Cleveland	Ohio	United States	44195
37	Ohio State University Medical Center Comprehensive Cancer Center	Columbus	Ohio	United States	43221
38	Oregon Health and Science University Oregon Health & Science U (56)	Portland	Oregon	United States	97239
39	Salem Health	Salem	Oregon	United States	97309
40	Fox Chase Cancer Center Dept of Medical Oncology	Philadelphia	Pennsylvania	United States	19111
41	Rhode Island Hospital Rhode Island Hosp. (2)	Providence	Rhode Island	United States	02903
42	Greenville Health System ITOR - Cancer Institute	Greenville	South Carolina	United States	29615
43	Sanford University of South Dakota Medical Center Sanford Health	Sioux Falls	South Dakota	United States	57104
44	Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology	Chattanooga	Tennessee	United States	37404
45	The West Clinic Dept. of the West Clinic	Memphis	Tennessee	United States	38120
46	Tennessee Oncology Tennessee Oncology (3)	Nashville	Tennessee	United States	37203
47	Coastal Bend Cancer Center	Corpus Christi	Texas	United States	78404
48	Oncology Consultants Oncology Group	Houston	Texas	United States	77024
49	MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)	Houston	Texas	United States	77030
50	University of Texas Health Science Center at San Antonio Cancer Therapy & Research Ctr.	San Antonio	Texas	United States	78229
51	Intermountain Medical Center Intermountain Healthcare	Murray	Utah	United States	84157
52	Utah Cancer Specialists Utah Cancer Specialists (11)	Salt Lake City	Utah	United States	84106
53	Shenandoah Oncology Shenadoah Oncology (2)	Winchester	Virginia	United States	22601
54	Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc	Kennewick	Washington	United States	99336
55	Vista Oncology Inc. PS	Olympia	Washington	United States	98502
56	Multicare Research Institute	Tacoma	Washington	United States	98405
57	Northwest Medical Specialties Rainier Physicians, PC	Tacoma	Washington	United States	98405
58	Providence St. Mary Regional Cancer Center	Walla Walla	Washington	United States	98057
59	Wenatchee Valley Medical Center Wenatchee Valley	Wenatchee	Washington	United States	98801
60	Aurora Research Institute Aurora Health Care	Milwaukee	Wisconsin	United States	53226
61	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Sep 27, 2015
• Study Protocol - Apr 10, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02187783
• Other Study ID Numbers: CLEE011XUS03
• First Posted: Jul 11, 2014
• Last Update Posted: Jul 18, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: 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
• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	There were 176 patients screened

Arm/Group Title	Ribociclib 600 mg
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

Baseline Characteristics

Arm/Group Title	Ribociclib 600 mg
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 Participants	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.5 (13.52)
Sex: Female, Male (Count of Participants)
Female	56 52.8%
Male	50 47.2%
Race/Ethnicity, Customized (Count of Participants)
White	90 84.9%
Black or African American	4 3.8%
Asian	5 4.7%
Other	7 6.6%
Primary tumor type (Count of 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%
Number of participants who had radiotherapy, surgery and liver metastasis (Count of 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 (participants) [Number]
Performance status = 0	36 34%
Performance status = 1	70 66%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ribociclib 600 mg
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.
Measure Participants	105
Complete response	0 0%
Partial response (PR)	3 2.8%
Stable disease (SD)	16 15.1%
Progressive disease (PD)	71 67%
Non-evaluable (NE)	15 14.2%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ribociclib 600 mg
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.
Measure Participants	105
Number (95% Confidence Interval) [participant]	19

3. Secondary Outcome

Title	Progression Free Survival (PFS)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ribociclib 600 mg
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.
Measure Participants	106
Median (95% Confidence Interval) [months]	1.8

4. Secondary Outcome

Title	Overall Survival (OS)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ribociclib 600 mg
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.
Measure Participants	106
Median (95% Confidence Interval) [months]	7.7

5. Secondary Outcome

Title	Number of Days for Duration of Response for Responders
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ribociclib 600 mg
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.
Measure Participants	3
Patient 1	254
Patient 2	330
Patient 3	985

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ribociclib 600 mg
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.
Measure Participants	105
Number (95% Confidence Interval) [participant]	3

Adverse Events

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.
Arm/Group Title	Ribociclib 600 mg
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 (%)	# Events
Total	14/106 (13.2%)
Serious Adverse Events
	Ribociclib 600 mg
	Affected / at Risk (%)	# Events
Total	40/106 (37.7%)
Blood and lymphatic system disorders
Anaemia	1/106 (0.9%)
Febrile neutropenia	1/106 (0.9%)
Thrombocytopenia	1/106 (0.9%)
Cardiac disorders
Atrial fibrillation	1/106 (0.9%)
Cardio-respiratory arrest	1/106 (0.9%)
Palpitations	1/106 (0.9%)
Pericardial effusion	2/106 (1.9%)
Gastrointestinal disorders
Abdominal pain	2/106 (1.9%)
Abdominal pain upper	1/106 (0.9%)
Ascites	1/106 (0.9%)
Constipation	1/106 (0.9%)
Dysphagia	1/106 (0.9%)
Haemorrhoids	1/106 (0.9%)
Mouth haemorrhage	1/106 (0.9%)
Nausea	3/106 (2.8%)
Small intestinal obstruction	2/106 (1.9%)
Vomiting	1/106 (0.9%)
General disorders
Asthenia	2/106 (1.9%)
Non-cardiac chest pain	1/106 (0.9%)
Pain	2/106 (1.9%)
Infections and infestations
Abscess	1/106 (0.9%)
Peritonitis	1/106 (0.9%)
Pneumonia	1/106 (0.9%)
Pseudomonal sepsis	1/106 (0.9%)
Pyelonephritis	1/106 (0.9%)
Pyelonephritis acute	1/106 (0.9%)
Sepsis	1/106 (0.9%)
Urinary tract infection	1/106 (0.9%)
Investigations
Alanine aminotransferase increased	1/106 (0.9%)
Aspartate aminotransferase increased	1/106 (0.9%)
Blood bilirubin increased	1/106 (0.9%)
Weight decreased	1/106 (0.9%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/106 (0.9%)
Failure to thrive	1/106 (0.9%)
Hypomagnesaemia	1/106 (0.9%)
Hyponatraemia	2/106 (1.9%)
Hypophosphataemia	1/106 (0.9%)
Malnutrition	1/106 (0.9%)
Musculoskeletal and connective tissue disorders
Bone pain	1/106 (0.9%)
Muscular weakness	1/106 (0.9%)
Pain in extremity	1/106 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/106 (0.9%)
Nervous system disorders
Aphasia	1/106 (0.9%)
Embolic stroke	1/106 (0.9%)
Transient ischaemic attack	1/106 (0.9%)
Psychiatric disorders
Confusional state	1/106 (0.9%)
Mental status changes	1/106 (0.9%)
Renal and urinary disorders
Nephropathy toxic	1/106 (0.9%)
Renal failure	1/106 (0.9%)
Renal tubular necrosis	1/106 (0.9%)
Ureteric obstruction	1/106 (0.9%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/106 (1.9%)
Dyspnoea	5/106 (4.7%)
Pulmonary embolism	1/106 (0.9%)
Respiratory failure	2/106 (1.9%)
Vascular disorders
Deep vein thrombosis	1/106 (0.9%)
Hypotension	1/106 (0.9%)
Thrombophlebitis superficial	1/106 (0.9%)
Other (Not Including Serious) Adverse Events
	Ribociclib 600 mg
	Affected / at Risk (%)	# Events
Total	104/106 (98.1%)
Blood and lymphatic system disorders
Anaemia	26/106 (24.5%)
Leukopenia	12/106 (11.3%)
Neutropenia	33/106 (31.1%)
Thrombocytopenia	13/106 (12.3%)
Gastrointestinal disorders
Abdominal pain	10/106 (9.4%)
Constipation	21/106 (19.8%)
Diarrhoea	28/106 (26.4%)
Dyspepsia	8/106 (7.5%)
Nausea	46/106 (43.4%)
Vomiting	31/106 (29.2%)
General disorders
Asthenia	8/106 (7.5%)
Chest pain	8/106 (7.5%)
Fatigue	45/106 (42.5%)
Oedema peripheral	12/106 (11.3%)
Pyrexia	8/106 (7.5%)
Infections and infestations
Urinary tract infection	11/106 (10.4%)
Investigations
Alanine aminotransferase increased	11/106 (10.4%)
Aspartate aminotransferase increased	11/106 (10.4%)
Blood alkaline phosphatase increased	8/106 (7.5%)
Blood creatinine increased	15/106 (14.2%)
Electrocardiogram QT prolonged	12/106 (11.3%)
Gamma-glutamyltransferase increased	9/106 (8.5%)
Lymphocyte count decreased	8/106 (7.5%)
Neutrophil count decreased	16/106 (15.1%)
Platelet count decreased	9/106 (8.5%)
Weight decreased	9/106 (8.5%)
White blood cell count decreased	19/106 (17.9%)
Metabolism and nutrition disorders
Decreased appetite	21/106 (19.8%)
Dehydration	7/106 (6.6%)
Hyperglycaemia	9/106 (8.5%)
Hypoalbuminaemia	7/106 (6.6%)
Hypokalaemia	7/106 (6.6%)
Hypomagnesaemia	9/106 (8.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/106 (7.5%)
Back pain	12/106 (11.3%)
Muscular weakness	7/106 (6.6%)
Musculoskeletal pain	8/106 (7.5%)
Myalgia	6/106 (5.7%)
Pain in extremity	7/106 (6.6%)
Nervous system disorders
Dizziness	13/106 (12.3%)
Headache	9/106 (8.5%)
Psychiatric disorders
Anxiety	7/106 (6.6%)
Confusional state	6/106 (5.7%)
Insomnia	11/106 (10.4%)
Renal and urinary disorders
Proteinuria	6/106 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	15/106 (14.2%)
Dyspnoea	20/106 (18.9%)
Epistaxis	6/106 (5.7%)
Oropharyngeal pain	6/106 (5.7%)
Skin and subcutaneous tissue disorders
Rash	6/106 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.