| Eligibility |
Inclusion Criteria:
1. Patient can and will sign the Informed Consent (ICF) prior to eligibility evaluations
being performed and is able to comply with treatment plan requirements
2. Patient is an adult and = 18 years old at the time of informed consent
3. Patient has locally advanced or metastatic HR+ breast cancer and no comparable or
satisfactory alternative therapy is available
4. PIK3CA mutation in tumor tissue or ctDNA as determined by a local laboratory
5. Patient is not:
1. eligible for participation in any ongoing clinical trials with alpelisib, or has
recently completed a clinical trial with alpelisib that has been terminated
2. being transferred from or participating in an ongoing clinical trial, and after
considering other options (e.g. trial extensions, amendments, etc.), treating
physician has determined that treatment is necessary and there are no other
feasible alternatives for the patient
6. Patient has adequate bone marrow and organ function as defined by the following
laboratory values:
1. Absolute Neutrophil Count (ANC) = 1.5 x 109/L
2. Platelets = 100 x 109/L (For patients with hematologic malignancies involving the
bone marrow, platelet count > 75 x 109/L may be acceptable)
3. Hemoglobin = 9.0 g/dL
4. INR = 1.5
5. Potassium, magnesium and calcium (corrected for albumin), within normal limits
for the institution, or = Grade 1 severity according to NCI-CTCAE version 4.03 if
judged clinically not significant by the investigator
6. Serum creatinine = 1.5 x ULN and/or creatinine clearance > 50% LLN (Lower Limit
of Normal)
7. Total serum bilirubin < ULN (or = 1.5 x ULN if liver metastases are present; or
total bilirubin = 3.0 x ULN with direct bilirubin within normal range in patients
with well documented Gilbert's 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)
8. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) = 2.5 ULN (or
< 5.0 x ULN if liver metastases are present)
9. Fasting plasma glucose (FPG) = 140mg/dL or = 7.7 mmol/L* or Glycosylated
Hemoglobin (HbA1c)= 6.4% (both criteria have to be met).
7. Patient is deemed by the Treating Physician to have the initiative and means to be
compliant with the treatment plan (treatment and follow-up requested by the Treating
Physician)
Exclusion Criteria:
1. Patient has history of hypersensitivity to any drugs or metabolites of PI3K inhibitor.
2. Patient has not recovered to grade 1 or better (except alopecia) from side effects of
any prior antineoplastic therapy
3. Patient has had major surgery within 14 days prior to starting treatment with
alpelisib or has not recovered from major side effects
4. Patient is currently receiving high doses of systemic corticosteroids = 2 weeks prior
to starting treatment with alpelisib, or has not fully recovered from side effects of
such treatment. (Note: low dose corticosteroids are permitted: single doses, topical
applications, inhaled sprays, eye applications or local injections, stable low dose,
for patients with CNS tumors, for at least 2 weeks prior to start of alpelisib
treatment.)
5. Patient with uncontrolled diabetes mellitus.
6. Patient is being treated at start of treatment with alpelisib with any of the
following drugs:
Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A4 including herbal
medications (list of prohibited CYP3A4 inhibitors and inducers provided in Table 13-2
in Appendix) Note: The patient must have discontinued strong inducers for at least one
week and must have discontinued strong inhibitors before the treatment with alpelisib
is initiated. Switching to a different medication prior to starting treatment with
alpelisib is allowed.
7. Patient is currently receiving warfarin or other coumarin derived anti-coagulant for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH), or fondaparinux is allowed. Patients receiving therapies listed in
Table 13-2 would not be allowed.
8. Patients who have other concurrent severe and/or uncontrolled medical conditions that
would, in the Treating Physician's judgment, contraindicate patient participation in
the individual patient program (eg. active or uncontrolled severe infection, chronic
active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high
blood pressure, interstitial lung disease, etc.)
9. Patient has a known history of Steven Johnson's syndrome or toxic epidermal necrolysis
10. Patient with active HIV infection (testing not mandatory) infection
11. Patient has any of the following cardiac abnormalities:
1. symptomatic congestive heart failure
2. history of documented congestive heart failure (New York Heart Association
functional classification III-IV), documented cardiomyopathy
3. Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO)
4. myocardial infarction = 6 months prior to enrolment
5. unstable angina pectoris
6. serious uncontrolled cardiac arrhythmia
7. symptomatic pericarditis
12. Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of alpelisib (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection)
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