EarLEE-1: Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03078751
• Collaborator: (none)
• Enrollment: 54
• Locations: 33
• Arms: 2
• Actual Duration (Months): 32.6
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an open label, multi-center protocol for U.S. patients enrolled in the study of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, high risk early breast cancer

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Ribociclib; Drug: Adjuvant endocrine therapy; Drug: Placebo	Phase 2

Detailed Description

The purpose of this study was to evaluate the preliminary safety and tolerability of ribociclib to standard adjuvant endocrine therapy (ET) in patients with hormone receptor (HR) positive, Human Epidermal Growth Factor Receptor2 (HER2) negative high risk early breast cancer (EBC).

Originally, this was a randomized, Phase III, double-blind, placebo-controlled, multi-center, international study to evaluate efficacy and safety of ribociclib with ET as an adjuvant treatment in patients with HR-positive, HER2-negative, high risk EBC.

Patients were randomized at a ratio of 1:1 to receive either ribociclib or placebo for approximately 24 months in combination with a standard adjuvant ET with ET continued for at least 60 months.

However, following a review of the ribociclib development program strategy, a decision was taken to explore a different approach by initiating a single Phase III study for simplicity of trial logistics and for the purpose of analyzing the overall population through a single clinical trial. Therefore, this study was closed to enrollment early and was amended to be an open label, multi-center Phase II study conducted in the US only. All randomized patients were unblinded; patients randomized to placebo were permanently discontinued from the study and patients randomized to ribociclib were offered the option to continue treatment with ribociclib + ET.

The study included a screening phase (28 days), a treatment phase composed of maximum of 26 cycles of ribociclib in combination with ET (approximately 24 months) or until disease recurrence, intolerable toxicity, withdrawal of consent, or discontinuation from the study treatment for any other reason, whichever was earlier, and a 30 days safety follow up from last dose of ribociclib. Ribociclib was given orally once a day on days 1 to 21 in each 28 days cycle.

Safety was assessed for each patient until 30 days after the last dose of ribociclib and included routine safety monitoring except in case of death, loss to follow up or withdrawal of consent.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: The trial used to be a placebo-controlled, blinded trial. It was amended to an open-label trial after protocol amendment 2.
• Primary Purpose: Treatment
• Official Title: An Open Label, Multi-center Protocol for U.S. Patients Enrolled in a Study of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, High Risk Early Breast Cancer
• Actual Study Start Date: Jun 20, 2017
• Actual Primary Completion Date: Mar 9, 2020
• Actual Study Completion Date: Mar 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ribociclib + adjuvant endocrine therapy (ET) Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)	Drug: Ribociclib; Ribociclib 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Ribociclib was supplied in the form of 200 mg film-coated tablets taken by mouth.; Other Names: LEE011 ; Drug: Adjuvant endocrine therapy; Letrozole 2.5 mg by mouth daily, or anastrozole 1 mg by mouth daily, exemestane 25 mg by mouth daily, tamoxifen 20 mg by mouth daily, for a total duration of at least 60 months. In premenopausal women, a GnRH agonist administered every 28 days.
Placebo Comparator: Placebo + adjuvant endocrine therapy (ET) Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen	Drug: Adjuvant endocrine therapy; Letrozole 2.5 mg by mouth daily, or anastrozole 1 mg by mouth daily, exemestane 25 mg by mouth daily, tamoxifen 20 mg by mouth daily, for a total duration of at least 60 months. In premenopausal women, a GnRH agonist administered every 28 days.; Drug: Placebo; Placebo 600 mg daily on days 1 to 21 of a 28-day cycle for 26 cycles (approximately 24 months). Placebo was supplied in the form of 200 mg film-coated tablets taken by mouth.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events and Serious Adverse Events [Up to 26 months]

   These are the number of participants who had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not

2. Percentage of Participants With Adverse Events and Serious Adverse Events [Up to 26 months]

   These are the percentage of participants that had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Histologically confirmed unilateral primary invasive adenocarcinoma of the breast

• Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer

• Patient is after surgical resection of the tumor where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen

• Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage Group III tumor; or patient who received neoadjuvant chemotherapy and have 1 or more ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue

• Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles or ≥ 12 weeks which included taxanes prior to screening

• Patient has completed adjuvant radiotherapy (if indicated) prior to screening

• Patient may already have initiated adjuvant endocrine therapy (ET) at the time of randomization, but randomization must take place within 52 weeks of date of initial histological diagnosis of breast cancer and within 12 weeks of initiating ET

• ECOG Performance Status 0 or 1

• Adequate bone marrow and organ function

• Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within normal limits

• QTcF interval < 450 msec and mean resting heart rate 50-90 bpm

Key Exclusion Criteria:

• Prior treatment with CDK4/6 inhibitor

• Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last 2 years

• Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin or 900 mg/m² or more for epirubicin

• Distant metastases of breast cancer beyond regional lymph nodes

• Patient has not recovered from clinical and laboratory acute toxicities of chemotherapy, radiotherapy and surgery

• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmias

• Uncontrolled hypertension with systolic blood pressure >160 mmHg

• Patient is currently receiving any of the prohibited substances that cannot be discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5; medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment; concomitant medications with a known risk to prolong the QT interval and/or known to cause torsades de points that cannot be discontinued or replaced by safe alternative medication.

• Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the study

• Women of child-bearing potential unless they are using highly effective methods of contraception during the study treatment and for 21 days after stopping the study treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates PC- HAL	Tucson	Arizona	United States	85704
2	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
3	CBCC Global Research	Bakersfield	California	United States	93309
4	University of California - Los Angeles	Los Angeles	California	United States	90024
5	Ventura County Hematology and Oncology	Oxnard	California	United States	93030
6	TRIO - Torrance Health Association	Redondo Beach	California	United States	90277
7	Innovative Clinical Research Institute	Whittier	California	United States	90603
8	Rocky Mountain Cancer Centers Regulatory	Denver	Colorado	United States	80218
9	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
10	Florida Cancer Specialists South Region	Fort Myers	Florida	United States	33916
11	Memorial Regional Hospital	Hollywood	Florida	United States	33021
12	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida	United States	34952
13	Florida Cancer Specialists - North Florida Cancer Specialist N	Saint Petersburg	Florida	United States	33705
14	Northside Hospital Central Research Dept.	Atlanta	Georgia	United States	30342
15	Summit Cancer Care, PC	Savannah	Georgia	United States	31405
16	Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Div.	Leawood	Kansas	United States	66209
17	Maryland Oncology Hematology P A	Silver Spring	Maryland	United States	20904
18	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
19	Saint Barnabas Medical Center 2nd Floor East Wing	Livingston	New Jersey	United States	07039
20	Pro Health Care Associates	New Hyde Park	New York	United States	11042
21	The Presbyterian Hospital	Charlotte	North Carolina	United States	28210
22	Tennessee Oncology, PLLC	Chattanooga	Tennessee	United States	37404
23	The West Clinic	Germantown	Tennessee	United States	38138
24	SCRI - Tennessee Oncology	Nashville	Tennessee	United States	37203
25	Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
26	Texas Oncology P A Texas Oncology - Houston	Dallas	Texas	United States	75251
27	Millennium Oncology	Houston	Texas	United States	77090
28	Cancer Care Network of South Texas	San Antonio	Texas	United States	78258
29	Texas Oncology PA - Tyler	Tyler	Texas	United States	75702
30	Fairfax Northern Virginia Hem/Onc	Fairfax	Virginia	United States	22031
31	Multicare Institute for Research and Innovation	Tacoma	Washington	United States	98405
32	Northwest Medical Specialties	Tacoma	Washington	United States	98405
33	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Apr 17, 2018
• Statistical Analysis Plan - Feb 24, 2020

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03078751
• Other Study ID Numbers: CLEE011G2301; 2014-001795-53
• First Posted: Mar 13, 2017
• Last Update Posted: Oct 11, 2021
• Last Verified: Oct 1, 2021

• 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: Hormone receptor-positive; Estrogen and/or progesterone receptor-positive; HER2-negative; High risk early breast cancer; Adjuvant; Ribociclib; LEE011; CDK4/6 inhibitor; Endocrine therapy; Phase II; Breast carcinoma; Breast cancer
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Recruitment Details

The study was closed early for recruitment and amended into an open-label, multi-centre, Phase II, conducted in the US only. A total of 54 patients were enrolled and randomized (26 in the ribociclib + ET arm and 28 in placebo + ET arm) at the time of recruitment closure. All randomized patients were unblinded. Patients randomized to placebo were permanently discontinued from the study and patients on ribociclib + ET were offered the option to continue treatment.

Pre-assignment Detail

Approximately 2000 patients were planned to be enrolled in the study.

Arm/Group Title	Ribociclib + Adjuvant Endocrine Therapy (ET)	Placebo + Adjuvant Endocrine Therapy (ET)
Arm/Group Description	Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)	Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
Period Title: Overall Study
STARTED	26	28
Untreated Participants	0	4
Safety Set	26	24
COMPLETED	13	0
NOT COMPLETED	13	28

Baseline Characteristics

Arm/Group Title	Ribociclib + Adjuvant Endocrine Therapy (ET)	Placebo + Adjuvant Endocrine Therapy (ET)	Total
Arm/Group Description	Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)	Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen	Total of all reporting groups
Overall Participants	26	28	54
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (11.23)	54.7 (9.04)	55.7 (10.11)
Sex: Female, Male (Count of Participants)
Female	26 100%	28 100%	54 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Asian	2 7.7%	3 10.7%	5 9.3%
Black	3 11.5%	4 14.3%	7 13%
Caucasian	18 69.2%	19 67.9%	37 68.5%
Other	2 7.7%	1 3.6%	3 5.6%
Unknown	1 3.8%	1 3.6%	2 3.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events
Description	These are the number of participants who had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not
Time Frame	Up to 26 months

Outcome Measure Data

Analysis Population Description

Safety set includes all patients who received at least one dose of any component of study treatment

Arm/Group Title	Ribociclib + Adjuvant Endocrine Therapy (ET)	Placebo + Adjuvant Endocrine Therapy (ET)
Arm/Group Description	Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)	Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
Measure Participants	26	24
Adverse Events	25 96.2%	21 75%
Serious Adverse Events	4 15.4%	2 7.1%

2. Primary Outcome

Title	Percentage of Participants With Adverse Events and Serious Adverse Events
Description	These are the percentage of participants that had adverse events or serious adverse events regardless of whether is was suspected to be drug-related or not
Time Frame	Up to 26 months

Outcome Measure Data

Analysis Population Description

Safety set includes all patients who received at least one dose of any component of study treatment

Arm/Group Title	Ribociclib + Adjuvant Endocrine Therapy (ET)	Placebo + Adjuvant Endocrine Therapy (ET)
Arm/Group Description	Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)	Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
Measure Participants	26	24
Adverse Events	96.2 370%	87.5 312.5%
Serious Adverse Events	15.4 59.2%	8.3 29.6%

Adverse Events

Time Frame	Time Frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment, up to maximum duration of approx. 26 months
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment plus 28 days post treatment.
Arm/Group Title	Ribociclib + Adjuvant Endocrine Therapy (ET)		Placebo + Adjuvant Endocrine Therapy (ET)
Arm/Group Description	Patients in this arm took Ribociclib in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen (Tamoxifen no longer permitted after protocol amendment 2)		Patients in this arm took Placebo in combination with standard adjuvant endocrine therapy. ET was one of these 4: Letrozole, Anastrozole, Exemestane, Tamoxifen
All Cause Mortality
	Ribociclib + Adjuvant Endocrine Therapy (ET)		Placebo + Adjuvant Endocrine Therapy (ET)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/24 (0%)
Serious Adverse Events
	Ribociclib + Adjuvant Endocrine Therapy (ET)		Placebo + Adjuvant Endocrine Therapy (ET)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/26 (15.4%)		2/24 (8.3%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/26 (3.8%)		0/24 (0%)
Cardiac disorders
Cardiac failure congestive	1/26 (3.8%)		0/24 (0%)
Infections and infestations
Breast cellulitis	1/26 (3.8%)		0/24 (0%)
Cellulitis	1/26 (3.8%)		1/24 (4.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/26 (3.8%)		0/24 (0%)
Nervous system disorders
Seizure	0/26 (0%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/26 (3.8%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Ribociclib + Adjuvant Endocrine Therapy (ET)		Placebo + Adjuvant Endocrine Therapy (ET)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/26 (96.2%)		19/24 (79.2%)
Blood and lymphatic system disorders
Anaemia	6/26 (23.1%)		1/24 (4.2%)
Leukopenia	2/26 (7.7%)		0/24 (0%)
Neutropenia	14/26 (53.8%)		0/24 (0%)
Thrombocytopenia	3/26 (11.5%)		0/24 (0%)
Cardiac disorders
Palpitations	2/26 (7.7%)		0/24 (0%)
Eye disorders
Vision blurred	2/26 (7.7%)		0/24 (0%)
Gastrointestinal disorders
Abdominal pain	5/26 (19.2%)		0/24 (0%)
Abdominal pain upper	3/26 (11.5%)		0/24 (0%)
Constipation	6/26 (23.1%)		0/24 (0%)
Diarrhoea	6/26 (23.1%)		1/24 (4.2%)
Gastrooesophageal reflux disease	4/26 (15.4%)		0/24 (0%)
Nausea	12/26 (46.2%)		6/24 (25%)
Stomatitis	3/26 (11.5%)		0/24 (0%)
Vomiting	4/26 (15.4%)		3/24 (12.5%)
General disorders
Axillary pain	1/26 (3.8%)		2/24 (8.3%)
Chest pain	2/26 (7.7%)		0/24 (0%)
Fatigue	12/26 (46.2%)		1/24 (4.2%)
Influenza like illness	2/26 (7.7%)		0/24 (0%)
Oedema peripheral	3/26 (11.5%)		1/24 (4.2%)
Pain	3/26 (11.5%)		0/24 (0%)
Pyrexia	4/26 (15.4%)		1/24 (4.2%)
Infections and infestations
Herpes zoster	2/26 (7.7%)		0/24 (0%)
Influenza	2/26 (7.7%)		2/24 (8.3%)
Nasopharyngitis	5/26 (19.2%)		0/24 (0%)
Pneumonia	2/26 (7.7%)		0/24 (0%)
Sinusitis	2/26 (7.7%)		2/24 (8.3%)
Upper respiratory tract infection	5/26 (19.2%)		1/24 (4.2%)
Urinary tract infection	3/26 (11.5%)		0/24 (0%)
Injury, poisoning and procedural complications
Contusion	2/26 (7.7%)		0/24 (0%)
Fall	2/26 (7.7%)		1/24 (4.2%)
Procedural pain	2/26 (7.7%)		0/24 (0%)
Investigations
Alanine aminotransferase increased	5/26 (19.2%)		0/24 (0%)
Aspartate aminotransferase increased	3/26 (11.5%)		0/24 (0%)
Blood calcium decreased	2/26 (7.7%)		0/24 (0%)
Blood cholesterol increased	2/26 (7.7%)		0/24 (0%)
Blood creatinine increased	4/26 (15.4%)		0/24 (0%)
Lymphocyte count decreased	4/26 (15.4%)		0/24 (0%)
Neutrophil count decreased	7/26 (26.9%)		0/24 (0%)
Weight increased	2/26 (7.7%)		0/24 (0%)
White blood cell count decreased	10/26 (38.5%)		0/24 (0%)
Metabolism and nutrition disorders
Hypokalaemia	2/26 (7.7%)		0/24 (0%)
Hypomagnesaemia	2/26 (7.7%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/26 (23.1%)		7/24 (29.2%)
Back pain	4/26 (15.4%)		1/24 (4.2%)
Bone pain	2/26 (7.7%)		0/24 (0%)
Muscle spasms	2/26 (7.7%)		1/24 (4.2%)
Musculoskeletal chest pain	4/26 (15.4%)		1/24 (4.2%)
Musculoskeletal pain	3/26 (11.5%)		2/24 (8.3%)
Myalgia	2/26 (7.7%)		4/24 (16.7%)
Neck pain	2/26 (7.7%)		0/24 (0%)
Pain in extremity	3/26 (11.5%)		1/24 (4.2%)
Nervous system disorders
Dizziness	4/26 (15.4%)		2/24 (8.3%)
Dysgeusia	2/26 (7.7%)		0/24 (0%)
Headache	5/26 (19.2%)		2/24 (8.3%)
Neuropathy peripheral	2/26 (7.7%)		0/24 (0%)
Psychiatric disorders
Confusional state	2/26 (7.7%)		0/24 (0%)
Insomnia	0/26 (0%)		2/24 (8.3%)
Renal and urinary disorders
Pollakiuria	2/26 (7.7%)		0/24 (0%)
Reproductive system and breast disorders
Breast pain	2/26 (7.7%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	7/26 (26.9%)		2/24 (8.3%)
Nasal congestion	2/26 (7.7%)		1/24 (4.2%)
Oropharyngeal pain	4/26 (15.4%)		1/24 (4.2%)
Productive cough	2/26 (7.7%)		0/24 (0%)
Rhinitis allergic	2/26 (7.7%)		0/24 (0%)
Upper respiratory tract congestion	2/26 (7.7%)		0/24 (0%)
Upper-airway cough syndrome	2/26 (7.7%)		0/24 (0%)
Wheezing	2/26 (7.7%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Alopecia	7/26 (26.9%)		1/24 (4.2%)
Rash	2/26 (7.7%)		1/24 (4.2%)
Vascular disorders
Hot flush	3/26 (11.5%)		3/24 (12.5%)
Lymphoedema	3/26 (11.5%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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 pooled data (i.e.,data from all sites) in clinical trial.