To check the Efficacy and Safety of Treatment With Alpelisib (BYL719) taken along with Endocrine Therapy in Patients With HR positive, HER2-negative advanced breast cancer, With PIK3CA Mutations, Whose Disease Has Progressed on or After CDK 4/6 Treatment With an Aromatase Inhibitor or Fulvestrant
- Conditions
- Health Condition 1: null- Breast Cancer
- Registration Number
- CTRI/2017/09/009687
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1. patient is male or female 18 years or older and has signed informed consent before any trial related activities and according to local guidelines
2. Patient is identified PIK3CA mutant status
3. Patient has confirmed HER2-negative advanced breast cancer (aBC)
4. Patient is postmenopausal woman defined as either: Prior bilateral oophorectomy; Age more than 60; Age less than 60 and amenorrhea for 12 or more months in the absence of chemotherapy,
tamoxifen, toremifen, or ovarian suppression and FSH and estradiol in the postmenopausal range per local normal range.
If patient is taking tamoxifen or toremifen and age less than 60, then FSH and plasma
estradiol levels should be in post menopausal range per local normal range.
5. Patients who received less than 14 days of tamoxifen or a NSAI letrozole or anastrozole with or without goserelin or goserelin less than 28 days for aBC prior to cohort assignment are eligible. Patients who are receiving goserelin for reasons other than for aBC treatment are eligible e.g. endometriosis. Patients who received less than 28 days goserelin for aBC are eligible.
6. Patient has histological and/or cytological confirmed ER+ and/or PgR positive aBC
7. Patients must be Diagnosed with aBC, with documented evidence of progression on or after CDK 4 6 inhibitor treatment For male patients, prior AI treatment is not required.
8. Patients must have either:
Measurable disease, i.e at least one measurable lesion as per RECIST v1.1 criteria
Tumor lesions previously irradiated or subjected to other locoregional therapy will only
be considered measurable if disease progression at the treated site after completion of
therapy is clearly documented.
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.
9. Patient has adequate bone marrow and coagulation function as shown by the following
laboratory values:
Absolute Neutrophil Count more than 1.5 x 109 per L
Platelets more than 100 x 109 per L For patients with hematologic malignancies involving thebone marrow, platelet count more than 75 x 109 per L may be acceptable
Hemoglobin more than 9.0 g per dL
INR less than 1.5 INR less than 2.0 will be allowed for those patients treated with vitamin K
antagonist
10. Patient has adequate liver function as shown by:
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5
ULN or less than 5 if hepatic metastases are present
Total serum bilirubin less than upper limit of normal or less than or equal to 1.5 x ULN if liver
metastases are present or total bilirubin less than or equal to 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilberts Syndrome, defined as
presence of several episodes of unconjugated hyperbilirubinemia with normal CBC
results including normal reticulocyte count and peripheral blood smear, normal liver
function test results, and absence of other contributing disease processes at the time of
diagnosis.
11. Patient has adequate rena
1. patient has received prior treatment with any PI3K inhibitors
2. Patients with central nervous system involvement unless they meet ALL of the
following criteria:
At least 4 weeks from prior therapy completion (including radiation and or surgery) to
starting the study treatment
Clinically stable CNS tumor at the time of screening untreated or without evidence of
progressions for at least 4 weeks after treatment as determined by clinical
examination and brain imaging MRI or CT during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
3. patient with clinically manifest diabetes mellitus, or documented steroid induced diabetes mellitus
4. Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non melanoma skin cancer or curatively resected cervical cancer
5. Patient has received radiotherapy less than 4 weeks or limited field radiation for palliation less than 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
6. Patient is currently receiving or has received systemic corticosteroids less than 2 weeks prior to starting treatment with alpelisib, or has not fully recovered from side effects of such
treatment
7. Patient has bilateral diffuse lymphangitic carcinomatosis
8. Patients with a known history of HIV seropositivity. Screening for HIV infection at
baseline is not required
9. Any severe and or uncontrolled medical conditions that would, in the investigators
judgment, contraindicate patient participation in the clinical study e.g chronic active
hepatitis, severe hepatic impairment, etc
10. Patients being treated with drugs recognized as being strong inhibitors or inducers of the
isoenzyme CYP3A Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Ietroconazole,
Voriconazole, Ritinavir, Telithromycin within the last 5 days prior to study entry
11. Patient has a history of noncompliance to medical regimens
12. Patient with severe liver impairment Child Pugh score B C
13. Patient has impairment of gastrointestinal 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
14. Patient has documented pneumonitis which is active and requiring treatment
15. Patient has not recovered from all toxicities related to prior anticancer therapies to NCI
CTCAE v4.03 Grade less than 1. Exception to this criterion patients with any grade of alopecia
are allowed to enter the study
16. Patient has had major surgery within 14 days prior to starting treatment with alpelisib or
has not recovered from major side effects
17. Patient has any of the following cardiac abnormalities:
a. symptomatic congestive heart failure
history of documented congestive heart failure New York Heart Association
functional classification III IV, documented cardiomyopathy
Left Ventricular Ejection Fraction <50% as determined by Multiple Gated
acquisition scan or echocardiogram
b. myocardial infarction less than 6 months prior to enrolment
c. unstable ang
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method