Clinical study to determine the efficacy and safety of alpelisib and fulvestrant in men andpostmenopausal women with advanced stage of breast cancer which progressed on or afterthe treatment of Aromatase Inhibitor.
- Conditions
- Health Condition 1: null- The study will include approximately 560 men and postmenopausal women with HR postive, HER2-negative advanced breast cancer whichprogressed on or after AI treatment.
- Registration Number
- CTRI/2016/06/007016
- Lead Sponsor
- ovartis Healthcare Private Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1. Patient is an adult = 18 years old at the time of informed consent and has signed informed
consent before any trial related activities and according to local guidelines.
2. Patient has adequate tumor tissue for the analysis of PIK3CA mutational status by a
Novartis designated laboratory. One new or recent biopsy(collected at screening if feasible) or archival tumor block or slides(15 slides
minimum from a surgical specimen, 20 slides minimum from a biopsy) must be provided. it is recommended to provide a tumor sample collected after the most recent progression or recurrence.
3. Patient has identified PIK3CA status (mutant or non-mutant; determined by a Novartis
designated laboratory).
4. If female, then the patient is postmenopausal. Postmenopausal status is defined either by:
a. Prior bilateral oophorectomy
b. Age less than or equal to 60
c. Age greater than 60 and amenorrheic for 12 or more months in the absence of chemotherapy,
tamoxifen, toremifene, or ovarian suppression and Follicle-stimulating Hormone
(FSH) and estradiol in the postmenopausal range per local normal range.
5. Patient has radiological or objective evidence of recurrence or progression.
6. Patient has a histologically and/or cytologically confirmed diagnosis of ER positive and/or PgR positive breast cancer by local laboratory.
7. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or
an IHC status of 0, 1 positive or 2 positive.If IHC is 2 positive,a negative in situ hybridization (FISH, CISH, or
SISH) test is required by local laboratory testing.
8. Patient has either:
a. Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (a
lesion at a previously irradiated site may only be counted as a target lesion if there is
clear sign of progression since the irradiation ) OR
b. If no measurable disease is present, then at last 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).
9. Patient has advanced (loco regionally recurrent not amenable to curative therapy or
metastatic) breast cancer.
Patients may be:
a.relapsed with documented evidence of progression while on or after
completion of (neo)adjuvant endocrine therapy with no treatment for metastatic
disease
b.relapsed with documented evidence of progression more than 12 months from
completion of adjuvant endocrine therapy and then subsequently progressed with
documented evidence of progression after one line of endocrine therapy for metastatic
disease
c.newly diagnosed advanced breast cancer, then relapsed with documented evidence of
progression while on or after one line of endocrine therapy.
10. Patient has recurrence or progression of disease during or after AI therapy (i.e. letrozole,
anastrozole, exemestane). AI therapy does not need to be the latest treatment regimen.
11. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
12. Patient has adequate bone marrow and organ function as defined by the following <br/
1. Patient with symptomatic visceral disease or any disease burden that makes the patientineligible for endocrine therapy per the investigator’s best judgment.
2. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant
chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor
3. Patient has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients
of alpelisib or fulvestrant.
4. Patient with inflammatory breast cancer at screening.
5. Patient is concurrently using other anti-cancer therapy.
6. Patient has had surgery within 14 days prior to starting study drug or has not recovered
from major side effects.
7. Patient has not recovered from all toxicities related to prior anticancer therapies to NCI
CTCAE version 4.03 Grade less than or equal to 1. Exception to this criterion: patients with any grade of
alopecia are allowed to enter the study.
8. Patients with Child pugh score B or C.
9. Patient has received radiotherapy less than or equal to 4 weeks or limited field radiation for palliation less than or equal to 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 from whom greater than or equal to 25percentage of
the bone marrow was irradiated.
10. 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.
11. Patients with an established diagnosis of diabetes mellitus type I or not controlled type II
(based on FPG and HbA1c, see inclusion criterion 12)
12. 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)
13. Patient has a known history of Human Immunodeficiency Virus (HIV) infection (testing
not mandatory)
14. 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 active hepatitis, severe hepatic impairment, etc.)
15. Patient has currently documented pneumonitis (the chest CT scan performed at baseline
for the purpose of tumor assessment should be reviewed to confirm that there are no
relevant pulmonary complications present).
16. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac events
including any of the following:
a.History of angina pectoris, coronary artery bypass graft (CABG) symptomatic pericarditis, or myocardial infarction within
12 months prior to study entry
b. History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
c. Documented cardiomyopathy
d.Patient has a Left Ventricular Ejection Fraction (LVEF) less than 50percentage as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
d.History of any cardiac arrhythmias, (e.g., ventricular tachycardia),complete left bundle block, high
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine whether treatment with alpelisib in combination with <br/ ><br>fulvestrant prolongs PFS compared to treatment with placebo in <br/ ><br>combination with fulvestrant for patients with PIK3CA mutant statusTimepoint: Time at which progression free survival is achieved.
- Secondary Outcome Measures
Name Time Method
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