Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01958021
• Collaborator: (none)
• Enrollment: 668
• Locations: 223
• Arms: 2
• Anticipated Duration (Months): 104.4
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, double-blinded, placebo controlled trial.

Condition or Disease	Intervention/Treatment	Phase
Advanced, Metastatic Breast Cancer	Drug: LEE011; Drug: Letrozole; Drug: LEE011 Placebo	Phase 3

Detailed Description

The primary purpose of this study was to assess the efficacy of LEE011, as measured by progression free survival (PFS), in postmenopausal women with HR positive, HER2 negative advanced breast cancer who received no prior treatment for advanced disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 668 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-blind, Placebo-controlled Study of LEE011 in Combination With Letrozole for the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
• Actual Study Start Date: Dec 17, 2013
• Actual Primary Completion Date: Jan 29, 2016
• Anticipated Study Completion Date: Aug 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LEE011 + letrozole LEE011 (Ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD	Drug: LEE011; Ribociclib was administered orally at a dose of 600 mg once daily (three 200 mg capsules).; Drug: Letrozole; Letrozole 2.5 mg tablets taken orally.
Placebo Comparator: Placebo + letrozole Matching ribociclib placebo was the control drug and was administered orally once daily.	Drug: Letrozole; Letrozole 2.5 mg tablets taken orally.; Drug: LEE011 Placebo; Matching ribociclib placebo was the control drug and was administered orally once daily.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Per Investigator Assessment [Up to approximately 20 months]

   PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1

Secondary Outcome Measures

1. Overall Response Rate (ORR) as Per Investigator Assessment [Up to approximately 20 months]

   Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

2. Overall Survival (OS) [Up to approximately 65 months]

   Time from date of randomization to the date of death from any cause.

3. Clinical Benefit Rate (CBR) [Up to approximately 20 months]

   Clinical Benefit Rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1.

4. Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score [Up to approximately 20.5 months]

   Time to definitive deterioration of ECOG performance status in one category of score is defined as the time from the date of randomization to the date of event, which is defined as at least one score lower than the baseline.

5. Safety and Tolerability of LEE011 [Up to approximately 21 months]

   Safety will be determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03.

6. Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [Up to approximately 20 months]

   The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause.

7. QTc Interval [Baseline, cycle 1 day 15, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1, cycle 6 day 1, cycle 7 day 1, cycle 8 day 1, cycle 9 day 1]

   Time between the start of the Q wave and the end of the T wave corrected for heart rate

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.

2. Patient is postmenopausal. Postmenopausal status is defined either by:

• Prior bilateral oophorectomy

• Age ≥60

• Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status. Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression in this trial.

1. No prior systemic anti-cancer therapy for advanced disease.

2. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.

3. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.

4. Patient must have either:

• Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other locoregional therapy will only be considered measurable if disease progression at the treated site after completion of therapy is clearly documented).

OR

• If no measurable disease is present, then at least one predominantly lytic bone lesion must be present (Patients with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).

1. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

1. Patient who received any CDK4/6 inhibitor.

2. Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer

Note:

• Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease free interval must be greater than 12 months from the completion of treatment until randomization.

• Patients who received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization are eligible.

• Any prior (neo) adjuvant anti-cancer therapy must be stopped at least 5 half-lives or 7 days, whichever is longer, before randomization

1. Patient is concurrently using other anti-cancer therapy.

2. Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.

3. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:

• History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry

• History of documented congestive heart failure (New York Heart Association functional classification III-IV)

• Documented cardiomyopathy

• Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)

• History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.

• On screening, any of the following cardiac parameters:

bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec.

• Systolic blood pressure >160 or <90 mmHg

1. Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior start if the treatment:

• That are known strong inducers or inhibitors of CYP3A4.

• That have a known risk to prolong the QT interval or induce Torsades de Pointes.

• That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.

• Herbal preparations/medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer and Research Centers SC	Chandler	Arizona	United States	85224
2	Arizona Oncology Associates PC HAL	Sedona	Arizona	United States	86336
3	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
4	NEA Baptist Cancer Center	Jonesboro	Arkansas	United States	72401
5	Alta Bates Cancer Center Oncology Dept.	Berkeley	California	United States	94704
6	City of Hope National Medical Center SC-5	Duarte	California	United States	91010 3000
7	Glendale-Adventist Medical Center Dept of Oncology	Glendale	California	United States	91206
8	The Angeles Clinic and Research Institute SC-3	Los Angeles	California	United States	90025
9	Cedars Sinai Medical Center SC-5	Los Angeles	California	United States	90048
10	UC Davis Comprehensive Cancer Center SC-2	Sacramento	California	United States	95817
11	University of Colorado School of Medicine Onc Dept.	Aurora	Colorado	United States	80045
12	Rocky Mountain Cancer Centers RMCC - Aurora	Longmont	Colorado	United States	80501
13	University Cancer Institute SC	Boynton Beach	Florida	United States	33426
14	Florida Cancer Research Institute Dept of Oncology	Davie	Florida	United States	33328
15	Florida Cancer Specialists FL Cancer Specialists	Fort Myers	Florida	United States	33901
16	Memorial Hospital SC	Hollywood	Florida	United States	33021
17	University of Miami Univ Miami 2	Miami	Florida	United States	33136
18	Florida Retina Institute SC-3	Orlando	Florida	United States	32804
19	Florida Retina Institute SC-5	Orlando	Florida	United States	32804
20	Sacred Heart Medical Oncology SC	Pensacola	Florida	United States	32504
21	Florida Cancer Specialists-North	Saint Petersburg	Florida	United States	33705
22	Georgia Cancer Specialists Georgia Cancer Spec	Decatur	Georgia	United States	30033
23	Lewis Hall Singletary Onc Ctr at John D. Archbold Mem Hosp. Onc Dept	Thomasville	Georgia	United States	31792
24	Moanalua Medical Center. Attn: Oncology Dept	Honolulu	Hawaii	United States	96817
25	University of Illinois Cancer Center at Chicago	Chicago	Illinois	United States	60612
26	University of Chicago Dept. of Oncology	Chicago	Illinois	United States	60637
27	North Shore University Health System	Evanston	Illinois	United States	60201
28	Ingalls Memorial Hospital Ingalls Mem Hosp	Harvey	Illinois	United States	60426
29	Edward Hospital Dept of Oncology	Naperville	Illinois	United States	60540
30	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
31	Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med SC-3	Baltimore	Maryland	United States	21231
32	Frederick Memorial Hospital SC	Frederick	Maryland	United States	21701
33	Dana Farber Cancer Institute Dana Farber-9	Boston	Massachusetts	United States	02215
34	Virginia Piper Cancer Institute, Allina Health	Minneapolis	Minnesota	United States	55407
35	Jackson Oncology Associates	Jackson	Mississippi	United States	39202
36	Saint Luke's Hospital/Marion Bloch Neuroscience Institute Oncology Dept	Kansas City	Missouri	United States	64111
37	Mercy Medical Research Institute SC-1	Manchester	Missouri	United States	63021
38	Foundation Medical Partners	Nashua	New Hampshire	United States	03060
39	Hackensack Meridian Health	Brick	New Jersey	United States	08724
40	Cooper Cancer Center Cooper Cancer Center	Camden	New Jersey	United States	08103
41	Cancer Institute of New Jersey Onc Dept	New Brunswick	New Jersey	United States	08901
42	Montefiore Medical Center SC-8	Bronx	New York	United States	10467
43	CR Wood Cancer Center	Glens Falls	New York	United States	12801
44	Winthrop University Hospital Onc Dept	Mineola	New York	United States	11501
45	NYU Langone Medical Center CV Research center SC-2	New York	New York	United States	10016
46	Mount Sinai School of Medicine SC	New York	New York	United States	10029
47	Duke University Medical Center SC-8	Durham	North Carolina	United States	27710
48	Oncology Hematology Care Inc Oncology Hematology Care (3)	Cincinnati	Ohio	United States	45242
49	The Ohio State University Comprehensive Cancer Center Ohio State-2	Columbus	Ohio	United States	43221
50	Mercy Clinic Oklahoma Communities Mercy Oncology	Oklahoma City	Oklahoma	United States	73120
51	Lehigh Valley Hospital Onc Dept	Allentown	Pennsylvania	United States	18103
52	Penn State University Milton S Hershey Medical Center SC-3	Hershey	Pennsylvania	United States	17033
53	Avera Cancer SC-2	Sioux Falls	South Dakota	United States	57105
54	Chattanooga Oncology and Hematology Associates PC Chattanooga Oncology	Chattanooga	Tennessee	United States	37404
55	Sarah Cannon Research Institute SC-2	Nashville	Tennessee	United States	37203
56	Vanderbilt University Medical Center SC-4	Nashville	Tennessee	United States	37232
57	Texas Oncology, P.A.	Bedford	Texas	United States	76022
58	Texas Oncology P A SC-3	Dallas	Texas	United States	75251
59	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
60	Center for Cancer and Blood Disorders SC	Fort Worth	Texas	United States	76104
61	Texas Oncology, P.A.	Fort Worth	Texas	United States	76104
62	Texas Oncology Houston Memorial City SC	Houston	Texas	United States	77024
63	University of Texas MD Anderson Cancer Center UT MDAnderson	Houston	Texas	United States	77030
64	Millennium Research Clin Develop SC	Houston	Texas	United States	77090
65	Texas Oncology	McAllen	Texas	United States	78503
66	Richardson Hematology Oncology Associates	Richardson	Texas	United States	75082
67	Texas Oncology P A	San Antonio	Texas	United States	78217
68	Texas Oncology Northeast Texas	Tyler	Texas	United States	75702
69	Utah Cancer Specialists Utah Cancer Specialists (11)	Salt Lake City	Utah	United States	84106
70	Virginia Cancer Specialists Fairfax Northern Virginia	Fairfax	Virginia	United States	22031
71	Oncology and Hematology Associates of Southwest Virginia Inc	Salem	Virginia	United States	24153
72	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
73	Northwest Medical Specialties Dept of Onc	Tacoma	Washington	United States	98405
74	Dean Health System Onc Dept	Madison	Wisconsin	United States	53717
75	Novartis Investigative Site	San Miguel De Tucuman	Tucuman	Argentina	T4000IAK
76	Novartis Investigative Site	Cordoba		Argentina	X5002AOQ
77	Novartis Investigative Site	La Rioja		Argentina	5300
78	Novartis Investigative Site	Kurralta Park	South Australia	Australia	5037
79	Novartis Investigative Site	East Melbourne	Victoria	Australia	3002
80	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
81	Novartis Investigative Site	Salzburg		Austria	5020
82	Novartis Investigative Site	Vienna		Austria	A-1100
83	Novartis Investigative Site	Wien		Austria	A-1090
84	Novartis Investigative Site	Sint Niklaas	Vlaams Brabant	Belgium	9100
85	Novartis Investigative Site	Hasselt		Belgium	3500
86	Novartis Investigative Site	Leuven		Belgium	3000
87	Novartis Investigative Site	Namur		Belgium	5000
88	Novartis Investigative Site	Wilrijk		Belgium	2610
89	Novartis Investigative Site	Ribeirao Preto	SP	Brazil	14048-900
90	Novartis Investigative Site	Sao Paulo	SP	Brazil	01246 000
91	Novartis Investigative Site	Sao Paulo	SP	Brazil	01317-002
92	Novartis Investigative Site	Burnaby	British Columbia	Canada	V5G 2X6
93	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 1V7
94	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
95	Novartis Investigative Site	Kitchener	Ontario	Canada	N2G 1G3
96	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
97	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
98	Novartis Investigative Site	Montreal	Quebec	Canada	H2W 1T8
99	Novartis Investigative Site	Quebec		Canada	G1S 4L8
100	Novartis Investigative Site	Brno Bohunice	Czech Republic	Czechia	625 00
101	Novartis Investigative Site	Brno	Czech Republic	Czechia	656 53
102	Novartis Investigative Site	Liberec	Czech Republic	Czechia	46063
103	Novartis Investigative Site	Olomouc	CZE	Czechia	775 20
104	Novartis Investigative Site	Aarhus		Denmark	DK-8000
105	Novartis Investigative Site	Copenhagen		Denmark	DK-2100
106	Novartis Investigative Site	Odense C		Denmark	DK 5000
107	Novartis Investigative Site	Vejle		Denmark	7100
108	Novartis Investigative Site	Helsinki		Finland	00029
109	Novartis Investigative Site	Turku		Finland	FIN-20520
110	Novartis Investigative Site	Nice Cedex 2	Alpes Maritimes	France	06189
111	Novartis Investigative Site	Villejuif Cedex	Villejuif	France	94800
112	Novartis Investigative Site	Angers Cedex 02		France	49055
113	Novartis Investigative Site	Avignon Cedex		France	84082
114	Novartis Investigative Site	Besancon Cedex		France	25030
115	Novartis Investigative Site	Bordeaux Cedex		France	33000
116	Novartis Investigative Site	Creteil		France	94000
117	Novartis Investigative Site	Le Mans Cedex		France	72015
118	Novartis Investigative Site	Lyon Cedex		France	69373
119	Novartis Investigative Site	Pierre Benite Cedex		France	69495
120	Novartis Investigative Site	Rouen Cedex 1		France	76038
121	Novartis Investigative Site	Saint-Herblain Cédex		France	44805
122	Novartis Investigative Site	Recklinghausen	North Rhine-westphalia	Germany	45657
123	Novartis Investigative Site	Aschaffenburg		Germany	63739
124	Novartis Investigative Site	Berlin		Germany	14169
125	Novartis Investigative Site	Berlin		Germany	14195
126	Novartis Investigative Site	Bielefeld		Germany	33604
127	Novartis Investigative Site	Bonn		Germany	53111
128	Novartis Investigative Site	Bottrop		Germany	46236
129	Novartis Investigative Site	Duesseldorf		Germany	40225
130	Novartis Investigative Site	Erlangen		Germany	91054
131	Novartis Investigative Site	Essen		Germany	45136
132	Novartis Investigative Site	Freiburg		Germany	79110
133	Novartis Investigative Site	Fuerth		Germany	90766
134	Novartis Investigative Site	Goslar		Germany	38642
135	Novartis Investigative Site	Heidelberg		Germany	69120
136	Novartis Investigative Site	Muenchen		Germany	80335
137	Novartis Investigative Site	Offenbach		Germany	63069
138	Novartis Investigative Site	Ravensburg		Germany	88214
139	Novartis Investigative Site	Tübingen		Germany	72076
140	Novartis Investigative Site	Ulm		Germany	89081
141	Novartis Investigative Site	Velbert		Germany	42551
142	Novartis Investigative Site	Budapest		Hungary	1134
143	Novartis Investigative Site	Debrecen		Hungary	4032
144	Novartis Investigative Site	Gyor		Hungary	H-9023
145	Novartis Investigative Site	Gyula		Hungary	5700
146	Novartis Investigative Site	Cork		Ireland
147	Novartis Investigative Site	Dublin 4		Ireland	4
148	Novartis Investigative Site	Petach Tikva		Israel	4941492
149	Novartis Investigative Site	Ramat Gan		Israel	52621
150	Novartis Investigative Site	Tel Aviv		Israel	6423906
151	Novartis Investigative Site	Brescia	BS	Italy	25123
152	Novartis Investigative Site	Genova	GE	Italy	16132
153	Novartis Investigative Site	Lecco	LC	Italy	23900
154	Novartis Investigative Site	Macerata	MC	Italy	62100
155	Novartis Investigative Site	Messina	ME	Italy	98158
156	Novartis Investigative Site	Milano	MI	Italy	20133
157	Novartis Investigative Site	Padova	PD	Italy	35100
158	Novartis Investigative Site	Perugia	PG	Italy	06129
159	Novartis Investigative Site	Pisa	PI	Italy	56126
160	Novartis Investigative Site	Aviano	PN	Italy	33081
161	Novartis Investigative Site	Reggio Calabria	RC	Italy	89124
162	Novartis Investigative Site	Roma	RM	Italy	00168
163	Novartis Investigative Site	Candiolo	TO	Italy	10060
164	Novartis Investigative Site	Terni	TR	Italy	05100
165	Novartis Investigative Site	Viterbo	VT	Italy	01100
166	Novartis Investigative Site	Napoli		Italy	80131
167	Novartis Investigative Site	Bundang Gu	Gyeonggi Do	Korea, Republic of	13620
168	Novartis Investigative Site	Gyeonggi do	Korea	Korea, Republic of	10408
169	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
170	Novartis Investigative Site	Seoul		Korea, Republic of	03080
171	Novartis Investigative Site	Seoul		Korea, Republic of	03722
172	Novartis Investigative Site	Ashrafieh		Lebanon	166830
173	Novartis Investigative Site	Beirut		Lebanon	1107 2020
174	Novartis Investigative Site	Beirut		Lebanon
175	Novartis Investigative Site	Saida		Lebanon	652
176	Novartis Investigative Site	Maastricht	AZ	Netherlands	5800
177	Novartis Investigative Site	Alkmaar		Netherlands	1815 JD
178	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
179	Novartis Investigative Site	Deventer		Netherlands	7416 SE
180	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
181	Novartis Investigative Site	Groningen		Netherlands	9728 NZ
182	Novartis Investigative Site	Leiden		Netherlands	2300 RC
183	Novartis Investigative Site	Sittard-Geleen		Netherlands	6162 BG
184	Novartis Investigative Site	Tilburg		Netherlands	5042 AD
185	Novartis Investigative Site	Zwolle		Netherlands	8025 AB
186	Novartis Investigative Site	Bergen		Norway	5021
187	Novartis Investigative Site	Oslo		Norway	0407
188	Novartis Investigative Site	Arkhangelsk		Russian Federation	163045
189	Novartis Investigative Site	Nizhniy Novgorod		Russian Federation
190	Novartis Investigative Site	Ryazan		Russian Federation	390011
191	Novartis Investigative Site	Singapore		Singapore	169610
192	Novartis Investigative Site	Pretoria	Gauteng	South Africa	0081
193	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
194	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
195	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
196	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
197	Novartis Investigative Site	Barcelona	Cataluña	Spain	08024
198	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46009
199	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
200	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife	Spain	38320
201	Novartis Investigative Site	Madrid		Spain	28009
202	Novartis Investigative Site	Madrid		Spain	28040
203	Novartis Investigative Site	Madrid		Spain	28041
204	Novartis Investigative Site	Madrid		Spain	28046
205	Novartis Investigative Site	Eskilstuna		Sweden	SE-631 88
206	Novartis Investigative Site	Goteborg		Sweden	413 45
207	Novartis Investigative Site	Joenkoeping		Sweden	551 85
208	Novartis Investigative Site	Lund		Sweden	221 85
209	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
210	Novartis Investigative Site	Vaxjo		Sweden	SE-351 85
211	Novartis Investigative Site	Kuei-Shan Chiang	Taoyuan/ Taiwan ROC	Taiwan	33305
212	Novartis Investigative Site	New Taipei City	TWN	Taiwan	23561
213	Novartis Investigative Site	Kaohsiung		Taiwan	80756
214	Novartis Investigative Site	Taipei		Taiwan	10048
215	Novartis Investigative Site	Taipei		Taiwan	11217
216	Novartis Investigative Site	Bangkok		Thailand	10330
217	Novartis Investigative Site	Ankara		Turkey	06100
218	Novartis Investigative Site	Ankara		Turkey	06590
219	Novartis Investigative Site	Diyarbakir		Turkey	21000
220	Novartis Investigative Site	Istanbul		Turkey	34303
221	Novartis Investigative Site	Izmir		Turkey	35040
222	Novartis Investigative Site	Truro	Cornwall	United Kingdom	TR1 3LJ
223	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE7 7DN

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01958021
• Other Study ID Numbers: CLEE011A2301; 2013-003084-61
• First Posted: Oct 8, 2013
• Last Update Posted: Aug 10, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: HR-positive; HER2-negative; Advanced breast cancer; LEE011; Letrozole; CDK; CDK4; CDK6; CDK4/6; Phase III; ER-positive; PR-positive; Postmenopausal
• Additional relevant MeSH terms: Breast Neoplasms; Letrozole

Study Results

Participant Flow

Pre-assignment Detail	Six-hundred and sixty-eight patients were randomized; 334 patients each to the ribociclib plus letrozole arm and the placebo plus letrozole arm. Four patients who were randomized to the placebo plus letrozole arm did not receive study treatment; three due to physician's decision and one due to subject/guardian decision.

Arm/Group Title	LEE011 + Letrozole	Placebo + Letrozole
Arm/Group Description	LEE011 (ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD	Matching ribociclib placebo, control drug administered orally (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 placebo QD + 2.5 mg letrozole
Period Title: Overall Study
STARTED	334	334
Patients Untreated	0	4
Patients Treated	334	330
COMPLETED	195	154
NOT COMPLETED	139	180

Baseline Characteristics

Arm/Group Title	LEE011 + Letrozole	Placebo + Letrozole	Total
Arm/Group Description	LEE011 (ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD	Matching ribociclib placebo, control drug administered orally (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 placebo QD + 2.5 mg letrozole	Total of all reporting groups
Overall Participants	334	334	668
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.4 (10.98)	61.9 (10.52)	61.6 (10.75)
Sex: Female, Male (Count of Participants)
Female	334 100%	334 100%	668 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Per Investigator Assessment
Description	PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1
Time Frame	Up to approximately 20 months

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS- population) consisted of all randomized patients.

Arm/Group Title	LEE011 + Letrozole	Placebo + Letrozole
Arm/Group Description	LEE011 (ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD	Matching ribociclib placebo, control drug administered orally (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 placebo QD + 2.5 mg letrozole
Measure Participants	334	334
Median (95% Confidence Interval) [months]	NA	14.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LEE011 + Letrozole, Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.00000329
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.556
	Confidence Interval	(2-Sided) 95%; 0.429 to 0.720
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Response Rate (ORR) as Per Investigator Assessment
Description	Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame	Up to approximately 20 months

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS- population) consisted of all randomized patients.

Arm/Group Title	LEE011 + Letrozole	Placebo + Letrozole
Arm/Group Description	LEE011 (ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD	Matching ribociclib placebo, control drug administered orally (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 placebo QD + 2.5 mg letrozole
Measure Participants	334	334
Number (95% Confidence Interval) [percentage of participants]	40.7 12.2%	27.5 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LEE011 + Letrozole, Placebo + Letrozole
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.000155
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Time from date of randomization to the date of death from any cause.
Time Frame	Up to approximately 65 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	Clinical Benefit Rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1.
Time Frame	Up to approximately 20 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score
Description	Time to definitive deterioration of ECOG performance status in one category of score is defined as the time from the date of randomization to the date of event, which is defined as at least one score lower than the baseline.
Time Frame	Up to approximately 20.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Safety and Tolerability of LEE011
Description	Safety will be determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03.
Time Frame	Up to approximately 21 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30
Description	The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause.
Time Frame	Up to approximately 20 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	QTc Interval
Description	Time between the start of the Q wave and the end of the T wave corrected for heart rate
Time Frame	Baseline, cycle 1 day 15, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1, cycle 6 day 1, cycle 7 day 1, cycle 8 day 1, cycle 9 day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Arm/Group Title	Ribociclib 600mg + Letrozole 2.5mg		Placebo + Letrozole 2.5mg
Arm/Group Description	LEE011 (ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD		Matching ribociclib placebo, control drug administered orally (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 placebo QD + 2.5 mg letrozole
All Cause Mortality
	Ribociclib 600mg + Letrozole 2.5mg		Placebo + Letrozole 2.5mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ribociclib 600mg + Letrozole 2.5mg		Placebo + Letrozole 2.5mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/334 (21.3%)		39/330 (11.8%)
Blood and lymphatic system disorders
ANAEMIA	4/334 (1.2%)		1/330 (0.3%)
FEBRILE NEUTROPENIA	4/334 (1.2%)		0/330 (0%)
LEUKOCYTOSIS	1/334 (0.3%)		0/330 (0%)
LEUKOPENIA	1/334 (0.3%)		0/330 (0%)
NEUTROPENIA	2/334 (0.6%)		0/330 (0%)
PANCYTOPENIA	1/334 (0.3%)		0/330 (0%)
THROMBOCYTOPENIA	1/334 (0.3%)		0/330 (0%)
Cardiac disorders
ARRHYTHMIA	1/334 (0.3%)		0/330 (0%)
ATRIAL FIBRILLATION	1/334 (0.3%)		0/330 (0%)
CARDIAC FAILURE CONGESTIVE	1/334 (0.3%)		0/330 (0%)
CARDIOMYOPATHY	1/334 (0.3%)		0/330 (0%)
CORONARY ARTERY DISEASE	0/334 (0%)		1/330 (0.3%)
Eye disorders
GLAUCOMA	0/334 (0%)		1/330 (0.3%)
Gastrointestinal disorders
ABDOMINAL DISTENSION	1/334 (0.3%)		0/330 (0%)
ABDOMINAL INCARCERATED HERNIA	1/334 (0.3%)		0/330 (0%)
ABDOMINAL PAIN	5/334 (1.5%)		0/330 (0%)
ABDOMINAL PAIN LOWER	0/334 (0%)		1/330 (0.3%)
ABDOMINAL PAIN UPPER	0/334 (0%)		1/330 (0.3%)
ASCITES	2/334 (0.6%)		0/330 (0%)
CONSTIPATION	4/334 (1.2%)		0/330 (0%)
DIARRHOEA	2/334 (0.6%)		0/330 (0%)
DUODENAL OBSTRUCTION	0/334 (0%)		1/330 (0.3%)
DUODENAL PERFORATION	1/334 (0.3%)		0/330 (0%)
DYSPEPSIA	0/334 (0%)		1/330 (0.3%)
FLATULENCE	1/334 (0.3%)		0/330 (0%)
GASTRIC ANTRAL VASCULAR ECTASIA	1/334 (0.3%)		0/330 (0%)
GASTROINTESTINAL WALL THICKENING	0/334 (0%)		1/330 (0.3%)
GASTROOESOPHAGEAL REFLUX DISEASE	0/334 (0%)		1/330 (0.3%)
HAEMATEMESIS	1/334 (0.3%)		0/330 (0%)
INGUINAL HERNIA	1/334 (0.3%)		0/330 (0%)
NAUSEA	4/334 (1.2%)		2/330 (0.6%)
OBSTRUCTION GASTRIC	1/334 (0.3%)		0/330 (0%)
VOMITING	5/334 (1.5%)		2/330 (0.6%)
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION	3/334 (0.9%)		1/330 (0.3%)
MALAISE	1/334 (0.3%)		0/330 (0%)
NON-CARDIAC CHEST PAIN	2/334 (0.6%)		0/330 (0%)
PYREXIA	2/334 (0.6%)		0/330 (0%)
SUDDEN DEATH	1/334 (0.3%)		0/330 (0%)
Hepatobiliary disorders
AUTOIMMUNE HEPATITIS	1/334 (0.3%)		0/330 (0%)
CHOLECYSTITIS	2/334 (0.6%)		0/330 (0%)
CHOLECYSTITIS ACUTE	1/334 (0.3%)		0/330 (0%)
HEPATIC FAILURE	2/334 (0.6%)		0/330 (0%)
HEPATOCELLULAR INJURY	1/334 (0.3%)		0/330 (0%)
HEPATOTOXICITY	3/334 (0.9%)		0/330 (0%)
Infections and infestations
BRONCHITIS	0/334 (0%)		1/330 (0.3%)
CELLULITIS	1/334 (0.3%)		1/330 (0.3%)
CLOSTRIDIUM DIFFICILE INFECTION	1/334 (0.3%)		0/330 (0%)
ERYSIPELAS	1/334 (0.3%)		0/330 (0%)
PNEUMONIA	3/334 (0.9%)		1/330 (0.3%)
PYELONEPHRITIS	0/334 (0%)		1/330 (0.3%)
PYELONEPHRITIS ACUTE	0/334 (0%)		1/330 (0.3%)
RETROPERITONEAL ABSCESS	0/334 (0%)		1/330 (0.3%)
SEPSIS	3/334 (0.9%)		0/330 (0%)
SKIN INFECTION	0/334 (0%)		1/330 (0.3%)
URINARY TRACT INFECTION	2/334 (0.6%)		0/330 (0%)
UROSEPSIS	1/334 (0.3%)		0/330 (0%)
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE	0/334 (0%)		1/330 (0.3%)
FEMUR FRACTURE	2/334 (0.6%)		0/330 (0%)
HIP FRACTURE	0/334 (0%)		1/330 (0.3%)
HUMERUS FRACTURE	1/334 (0.3%)		0/330 (0%)
INFLAMMATION OF WOUND	0/334 (0%)		1/330 (0.3%)
OVERDOSE	1/334 (0.3%)		0/330 (0%)
RADIUS FRACTURE	1/334 (0.3%)		0/330 (0%)
SPINAL COMPRESSION FRACTURE	0/334 (0%)		2/330 (0.6%)
SPINAL FRACTURE	1/334 (0.3%)		0/330 (0%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	4/334 (1.2%)		0/330 (0%)
ASPARTATE AMINOTRANSFERASE INCREASED	3/334 (0.9%)		0/330 (0%)
BLOOD BILIRUBIN INCREASED	1/334 (0.3%)		0/330 (0%)
BLOOD CREATININE INCREASED	1/334 (0.3%)		0/330 (0%)
BLOOD THYROID STIMULATING HORMONE DECREASED	0/334 (0%)		1/330 (0.3%)
LYMPHOCYTE COUNT DECREASED	1/334 (0.3%)		0/330 (0%)
NEUTROPHIL COUNT DECREASED	1/334 (0.3%)		0/330 (0%)
TRANSAMINASES INCREASED	1/334 (0.3%)		0/330 (0%)
WAIST CIRCUMFERENCE INCREASED	1/334 (0.3%)		0/330 (0%)
WEIGHT DECREASED	1/334 (0.3%)		0/330 (0%)
WHITE BLOOD CELL COUNT DECREASED	1/334 (0.3%)		0/330 (0%)
Metabolism and nutrition disorders
DECREASED APPETITE	1/334 (0.3%)		0/330 (0%)
DEHYDRATION	2/334 (0.6%)		1/330 (0.3%)
ELECTROLYTE IMBALANCE	1/334 (0.3%)		0/330 (0%)
HYPERCALCAEMIA	0/334 (0%)		1/330 (0.3%)
HYPOGLYCAEMIA	1/334 (0.3%)		0/330 (0%)
HYPOKALAEMIA	0/334 (0%)		1/330 (0.3%)
HYPOPHOSPHATAEMIA	1/334 (0.3%)		0/330 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/334 (0.3%)		0/330 (0%)
BACK PAIN	3/334 (0.9%)		1/330 (0.3%)
BONE PAIN	1/334 (0.3%)		0/330 (0%)
HAEMARTHROSIS	1/334 (0.3%)		0/330 (0%)
PATHOLOGICAL FRACTURE	0/334 (0%)		1/330 (0.3%)
SPINAL PAIN	1/334 (0.3%)		0/330 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	0/334 (0%)		1/330 (0.3%)
BLADDER CANCER	1/334 (0.3%)		0/330 (0%)
MALIGNANT MELANOMA IN SITU	1/334 (0.3%)		0/330 (0%)
MENINGIOMA	0/334 (0%)		1/330 (0.3%)
METASTASES TO CENTRAL NERVOUS SYSTEM	0/334 (0%)		1/330 (0.3%)
METASTASES TO MENINGES	1/334 (0.3%)		0/330 (0%)
ONCOCYTOMA	1/334 (0.3%)		0/330 (0%)
SQUAMOUS CELL CARCINOMA	1/334 (0.3%)		0/330 (0%)
TUMOUR PAIN	0/334 (0%)		1/330 (0.3%)
UTERINE LEIOMYOMA	1/334 (0.3%)		0/330 (0%)
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUSNESS	1/334 (0.3%)		0/330 (0%)
DIZZINESS	3/334 (0.9%)		0/330 (0%)
EPILEPSY	0/334 (0%)		1/330 (0.3%)
HAEMORRHAGE INTRACRANIAL	0/334 (0%)		1/330 (0.3%)
HEADACHE	0/334 (0%)		1/330 (0.3%)
MIGRAINE	1/334 (0.3%)		0/330 (0%)
PARAESTHESIA	0/334 (0%)		1/330 (0.3%)
SPINAL CORD COMPRESSION	1/334 (0.3%)		1/330 (0.3%)
SYNCOPE	3/334 (0.9%)		0/330 (0%)
Psychiatric disorders
CONFUSIONAL STATE	1/334 (0.3%)		0/330 (0%)
MENTAL STATUS CHANGES	2/334 (0.6%)		1/330 (0.3%)
Renal and urinary disorders
ACUTE KIDNEY INJURY	1/334 (0.3%)		1/330 (0.3%)
RENAL FAILURE	1/334 (0.3%)		1/330 (0.3%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	1/334 (0.3%)		0/330 (0%)
DYSPNOEA	4/334 (1.2%)		1/330 (0.3%)
HYPOXIA	1/334 (0.3%)		0/330 (0%)
PLEURAL EFFUSION	2/334 (0.6%)		4/330 (1.2%)
PLEURAL FIBROSIS	1/334 (0.3%)		0/330 (0%)
PNEUMOTHORAX	1/334 (0.3%)		0/330 (0%)
PULMONARY EMBOLISM	2/334 (0.6%)		0/330 (0%)
PULMONARY HAEMORRHAGE	1/334 (0.3%)		0/330 (0%)
PULMONARY OEDEMA	1/334 (0.3%)		0/330 (0%)
Skin and subcutaneous tissue disorders
ERYTHEMA	1/334 (0.3%)		0/330 (0%)
Vascular disorders
HYPERTENSION	0/334 (0%)		1/330 (0.3%)
HYPOTENSION	2/334 (0.6%)		0/330 (0%)
ORTHOSTATIC HYPOTENSION	1/334 (0.3%)		0/330 (0%)
SUBCLAVIAN VEIN THROMBOSIS	0/334 (0%)		1/330 (0.3%)
Other (Not Including Serious) Adverse Events
	Ribociclib 600mg + Letrozole 2.5mg		Placebo + Letrozole 2.5mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	329/334 (98.5%)		308/330 (93.3%)
Blood and lymphatic system disorders
ANAEMIA	59/334 (17.7%)		15/330 (4.5%)
LEUKOPENIA	51/334 (15.3%)		9/330 (2.7%)
NEUTROPENIA	203/334 (60.8%)		14/330 (4.2%)
THROMBOCYTOPENIA	19/334 (5.7%)		2/330 (0.6%)
Ear and labyrinth disorders
VERTIGO	17/334 (5.1%)		5/330 (1.5%)
Eye disorders
DRY EYE	19/334 (5.7%)		7/330 (2.1%)
LACRIMATION INCREASED	23/334 (6.9%)		6/330 (1.8%)
Gastrointestinal disorders
ABDOMINAL PAIN	30/334 (9%)		25/330 (7.6%)
ABDOMINAL PAIN UPPER	21/334 (6.3%)		18/330 (5.5%)
CONSTIPATION	80/334 (24%)		63/330 (19.1%)
DIARRHOEA	117/334 (35%)		73/330 (22.1%)
DRY MOUTH	32/334 (9.6%)		31/330 (9.4%)
DYSPEPSIA	22/334 (6.6%)		14/330 (4.2%)
NAUSEA	171/334 (51.2%)		93/330 (28.2%)
STOMATITIS	41/334 (12.3%)		22/330 (6.7%)
VOMITING	95/334 (28.4%)		50/330 (15.2%)
General disorders
ASTHENIA	43/334 (12.9%)		38/330 (11.5%)
FATIGUE	122/334 (36.5%)		99/330 (30%)
INFLUENZA LIKE ILLNESS	16/334 (4.8%)		18/330 (5.5%)
NON-CARDIAC CHEST PAIN	14/334 (4.2%)		21/330 (6.4%)
OEDEMA PERIPHERAL	41/334 (12.3%)		33/330 (10%)
PYREXIA	40/334 (12%)		18/330 (5.5%)
Infections and infestations
INFLUENZA	18/334 (5.4%)		12/330 (3.6%)
NASOPHARYNGITIS	25/334 (7.5%)		19/330 (5.8%)
UPPER RESPIRATORY TRACT INFECTION	35/334 (10.5%)		35/330 (10.6%)
URINARY TRACT INFECTION	35/334 (10.5%)		27/330 (8.2%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	50/334 (15%)		13/330 (3.9%)
ASPARTATE AMINOTRANSFERASE INCREASED	49/334 (14.7%)		12/330 (3.6%)
BLOOD ALKALINE PHOSPHATASE INCREASED	15/334 (4.5%)		18/330 (5.5%)
BLOOD CREATININE INCREASED	23/334 (6.9%)		3/330 (0.9%)
LYMPHOCYTE COUNT DECREASED	21/334 (6.3%)		3/330 (0.9%)
NEUTROPHIL COUNT DECREASED	63/334 (18.9%)		3/330 (0.9%)
WEIGHT DECREASED	20/334 (6%)		11/330 (3.3%)
WHITE BLOOD CELL COUNT DECREASED	63/334 (18.9%)		5/330 (1.5%)
Metabolism and nutrition disorders
DECREASED APPETITE	61/334 (18.3%)		50/330 (15.2%)
HYPERGLYCAEMIA	17/334 (5.1%)		14/330 (4.2%)
HYPOCALCAEMIA	17/334 (5.1%)		6/330 (1.8%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	91/334 (27.2%)		95/330 (28.8%)
BACK PAIN	66/334 (19.8%)		58/330 (17.6%)
BONE PAIN	23/334 (6.9%)		35/330 (10.6%)
MUSCLE SPASMS	11/334 (3.3%)		19/330 (5.8%)
MUSCULOSKELETAL CHEST PAIN	16/334 (4.8%)		22/330 (6.7%)
MUSCULOSKELETAL PAIN	26/334 (7.8%)		39/330 (11.8%)
MYALGIA	22/334 (6.6%)		21/330 (6.4%)
PAIN IN EXTREMITY	35/334 (10.5%)		40/330 (12.1%)
Nervous system disorders
DIZZINESS	39/334 (11.7%)		43/330 (13%)
DYSGEUSIA	31/334 (9.3%)		19/330 (5.8%)
HEADACHE	74/334 (22.2%)		63/330 (19.1%)
Psychiatric disorders
ANXIETY	26/334 (7.8%)		20/330 (6.1%)
DEPRESSION	24/334 (7.2%)		23/330 (7%)
INSOMNIA	39/334 (11.7%)		31/330 (9.4%)
Reproductive system and breast disorders
BREAST PAIN	15/334 (4.5%)		22/330 (6.7%)
Respiratory, thoracic and mediastinal disorders
COUGH	65/334 (19.5%)		59/330 (17.9%)
DYSPNOEA	37/334 (11.1%)		28/330 (8.5%)
OROPHARYNGEAL PAIN	19/334 (5.7%)		15/330 (4.5%)
Skin and subcutaneous tissue disorders
ALOPECIA	111/334 (33.2%)		51/330 (15.5%)
DRY SKIN	27/334 (8.1%)		10/330 (3%)
PRURITUS	45/334 (13.5%)		19/330 (5.8%)
RASH	57/334 (17.1%)		26/330 (7.9%)
Vascular disorders
HOT FLUSH	70/334 (21%)		78/330 (23.6%)
HYPERTENSION	48/334 (14.4%)		49/330 (14.8%)

Limitations/Caveats

Four patients who were randomized to the placebo plus letrozole arm did not receive study treatment and so are not part of the Safety Set.

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.