Study of Efficacy and Safety of LEE011 in Premenopausal Women With Advanced Breast Cancer

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2014-001931-36-BG
• Date of registration: 12/01/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• 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: 09/03/2015
• Target sample size: 660
• Recruitment status: Not Recruiting
• 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: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, 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: Clinical Trials Information
• Affiliation: Novartis Pharma Services AG

• Name: Clinical Trials Information
• Affiliation: Novartis Pharma Services AG

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) 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.
• if tamoxifen or fulvestrant 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 a NSAI (letrozole or anastrazole) +
goserelin for advanced breast cancer.
• If letrozole, anastrozole, 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 or goserelin <= 28 days 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.
Note: Patients receiving goserelin for reasons other than for advanced
breast cancer treatment are eligible (e.g. endometriosis). Patients who
received <= 28 days goserelin for advanced breast cancer are eligible.
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.
Note: if a cytotoxic chemotherapy regimen was discontinued for reasons
other than disease progression and lasted less than 21 d, this regimen
does not count as a prior line of chemotherapy.
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. Pat
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 or
goserelin >= days 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.
Note: CNS involvement must be ruled out by assessments if a patient has
any signs or symptoms indicating potential 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. Clinically significant, uncontrolled hearth disease and/or recent
cardiac events
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 or goserelin
<= 28 days 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 and for 21 days

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

premenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer
MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864

Intervention(s)

Product Name: ribociclib
Product Code: LEE011
Pharmaceutical Form: Capsule, hard
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
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
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
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
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)

Secondary Objective: Key secondary:
To determine whether treatment with tamoxifen/NSAI + goserelin + LEE011 prolongs OS compared to treatment with tamoxifen/NSAI + goserelin + placebo

Timepoint(s) of evaluation of this end point: median PFS of 13.4 months

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)

Timepoint(s) of evaluation of this end point: median OS of 47 months

Secondary end point(s): Key secondary:
Overall Survival (OS)

Secondary ID(s)

2014-001931-36-HU

CLEE011E2301

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 09/03/2015
Contact: