Study of Efficacy and Safety of LEE011 in Premenopausal Women With Advanced Breast Cancer
- Conditions
- premenopausal women with hormone receptor positive, HER2-negative, advanced breast cancerMedDRA version: 17.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001931-36-IT
- Lead Sponsor
- OVARTIS FARMA S.p.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 660
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method