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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 10 July 2015
Main ID:  EUCTR2014-001931-36-IT
Date of registration: 28/11/2014
Prospective Registration: Yes
Primary sponsor: NOVARTIS FARMA S.p.A.
Public title: Study of Efficacy and Safety of LEE011 in Premenopausal Women With Advanced Breast Cancer
Scientific title: A Phase III randomized, double-blind, placebo-controlled study of LEE011 or placebo in combination with tamoxifen and goserelin or a non-steroidal aromatase inhibitor (NSAI) and goserelin for the treatment of premenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer - Monaleesa-7
Date of first enrolment: 09/02/2015
Target sample size: 660
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001931-36
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2  
Phase: 
Countries of recruitment
Argentina Australia Austria Belgium Brazil Bulgaria Canada China
Colombia Czech Republic Denmark Finland France Germany Greece Hong Kong
Hungary India Israel Italy Japan Jordan Korea, Republic of Lebanon
Mexico Norway Poland Portugal Russian Federation Saudi Arabia Singapore Slovakia
South Africa Spain Sweden Switzerland Taiwan Thailand Turkey United Arab Emirates
United Kingdom United States
Contacts
Name: Drug Regulatory Affairs   
Address:  Largo Umberto Boccioni, 1 21040 ORIGGIO Italy
Telephone: +390296541
Email: info.studiclinici@novartis.com
Affiliation:  NOVARTIS FARMA S.p.A.
Name: Drug Regulatory Affairs   
Address:  Largo Umberto Boccioni, 1 21040 ORIGGIO Italy
Telephone: +390296541
Email: info.studiclinici@novartis.com
Affiliation:  NOVARTIS FARMA S.p.A.
Key inclusion & exclusion criteria
Inclusion criteria:
1. Patient is an adult, female = 18 years old and < 60 years old at the time of informed consent and has signed informed consent before any trial related activities are conducted and according to local guidelines.
2. Confirmed negative serum pregnancy test (ß-hCG) within 72 hrs before starting study treatment.
3. Patient is premenopausal or perimenopausal at the time of study entry.
4. Patient has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy (e.g. surgery and/or radiotherapy).
5. Patients who received (neo) adjuvant therapy for breast cancer are eligible:
• If the patient has never received any prior endocrine therapy OR if = 12 months have elapsed since the patient’s last dose of adjuvant therapy, then the patient is eligible to receive tamoxifen + goserelin OR a NSAI + goserelin for advanced breast cancer based on the investigator’s choice.
• 12 months prior to randomization, then the patient is eligible to receive a NSAI (letrozole or anastrazole) + goserelin for advanced breast cancer.
• If letrozole, anastrozole, fulvestrant, or exemestane was the last prior (neo) adjuvant therapy and the last dose was given < 12 months prior to randomization, then the patient is eligible to receive tamoxifen + goserelin for advanced breast cancer.
Note: Prior (neo) adjuvant anti-cancer therapy must be stopped at least 5 half-lives or 7 days before randomization, whichever is longer.
6. Patients who received = 14 days of tamoxifen or a NSAI (letrozole or anastrozole) with or without goserelin for advanced breast cancer prior to randomization are eligible. Patients must continue treatment with the same hormonal agent + goserelin during the study. No treatment interruption is required for these patients prior to randomization.
7. Patients who have received up to 1 line of chemotherapy for advanced breast cancer and have been discontinued 28 days before randomization are eligible.
8. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory (based on most recently analyzed biopsy).
9. Patient has HER2-negative breast cancer (based on most recently analyzed biopsy) 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.
10. Patient must have either:
• Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria.
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).
11. Patient has ECOG PS 0 or 1.
12. Patient has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by central laboratory).

Other inclusion criteria as per full protocol may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 660
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Patient who has received a prior CDK4/6 inhibitor.
2. Patient has a known hypersensitivity to any of the excipients of LEE011 or goserelin or hormonal treatment assigned (tamoxifen, NSAI (letrozole or anastrozole)).
3. Patient is postmenopausal.
4. Patients who currently have inflammatory breast cancer on screening.
5. Patient who received any prior hormonal anti-cancer therapy for advanced breast cancer, except for = 14 days of tamoxifen or NSAI ± goserelin for advanced breast cancer prior to randomization.
6. Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 4.03 Grade =1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
7. Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal cell skin carcinoma, squamous cell skin carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
8. Patient with CNS metastases.
9. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
10. Patient has a known history of HIV infection (testing not mandatory)
11. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, contraindicate patient participation in the clinical study (e.g., chronic pancreatitis, chronic active hepatitis, etc.)
12. Patient has active cardiac disease or a history of cardiac dysfunction
13. Patient is currently receiving any of the substances described in the protocol and cannot be discontinued 7 days prior to the start of the treatment.
14. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
15. Patient is currently receiving warfarin or other Coumadin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
16. Patient is currently receiving or has received systemic corticosteroids = 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
17. Patient is concurrently using other antineoplastic agents (except for patients who are receiving = 14 days of tamoxifen or NSAI ± goserelin for advanced breast cancer prior to randomization).
18. Patient who has received radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or if = 25% of the bone marrow was irradiated.
19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. Highly effective contraception methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptother


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no
Health Condition(s) or Problem(s) studied
premenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer
MedDRA version: 17.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Intervention(s)

Product Code: LEE011
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LEE011
CAS Number: 1374639-75-4
Current Sponsor code: LEE011
Other descriptive name: LEE011
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Femara
Product Name: letrozole
Pharmaceutical Form: Tablet
INN or Proposed INN: LETROZOLE
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Zoladex
Product Name: Goserelin
Pharmaceutical Form: Implant
INN or Proposed INN: goserelin
CAS Number: 65807-02-5
Other descriptive name: GOSERELIN ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.6-

Trade Name: Nolvadex
Product Name: Tamoxifene
Pharmaceutical Form: Tablet
INN or Proposed INN: tamoxifen
CAS Number: 10540-29-1
Other descriptive name: TAMOXIFEN CITRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Arimidex
Product Name: Anastrozolo
Pharmaceutical Form: Tablet
INN or Proposed INN: anastrozole
CAS Number: 120511-73-1
Other descriptive name: ANASTROZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)
Timepoint(s) of evaluation of this end point: median PFS of 13.4 months
Secondary Objective: Key secondary:
To determine whether treatment with tamoxifen/NSAI + goserelin + LEE011 prolongs OS compared to treatment with tamoxifen/NSAI + goserelin + placebo
Main Objective: To determine whether treatment with tamoxifen/NSAI + goserelin + LEE011 prolongs PFS compared to treatment with tamoxifen/NSAI + goserelin + placebo in premenopausal women with HR+, HER2-negative breast cancer
Primary end point(s): PFS per local assessment and RECIST 1.1
Secondary Outcome(s)
Secondary end point(s): Key secondary:
Overall Survival (OS)
Timepoint(s) of evaluation of this end point: median OS of 47 months
Secondary ID(s)
CLEE011E2301
2014-001931-36-HU
Source(s) of Monetary Support
Novartis Pharma Services AG
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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