Official Title
Managed Access Program (MAP)* to Provide Access to Alpelisib, in Combination With Fulvestrant (ET) in Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer With a PIK3CA Mutation After Disease Progression Following a CDK4/6 Inhibitors
Brief Summary

The purpose of this Cohort Treatment Plan is to allow access to alpelisib in combination with fulvestrant in postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer with a PIK3CA mutation after disease progression following a CDK 4/6 inhibitors; according to physician's judgement there are no therapeutic alternatives available for patients in this setting. The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations

Intermediate-size Population
Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer With a PIK3CA Mutation

Drug: alpelisib + fulvestrant
Alpelisib will be provided as 50 mg and 200 mg film coated tablets as individual patient supply and will be dosed on a flat scale of mg/day. Alpelisib will be administered at a starting dose of 300 mg orally once daily on a continuous dosing schedule and can be adjusted for toxicity per the recommendations in this treatment plan. Fulvestrant will not be provided by Novartis

Eligibility Criteria

Inclusion Criteria:

Patients eligible for inclusion in this Treatment Plan have to meet all of the following

Written patient informed consent must be obtained prior to start of treatment.

1. Patient is an adult female (≥ 18 years of age) with advanced (locoregionally recurrent not amenable to curative therapy or metastatic) hormone receptor-positive, HER2-negative breast cancer

2. Patient has documented evidence of a mutation in the PIK3CA gene as determined in tumor tissue or plasma by a local laboratory.

3. The patient is postmenopausal. Postmenopausal status is defined either by: - Prior bilateral oophorectomy - Age ≥60 - Age 50% LLN 7. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. If the patient has liver metastases, ALT and AST ≤ 5 × ULN 8. Total serum bilirubin < ULN (or ≤ 1.5 × ULN if liver metastases are present, or total bilirubin ≤ 3.0 × ULN and direct bilirubin in normal range for patients with Gilbert's syndrome) 9. Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L)* and Glycosylated Hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met) *For patients with FPG ≥ 100 mg/dL and/or HbA1c ≥5.7% (i.e. threshold for prediabetes), recommend lifestyle changes according to ADA or similar local diabetes guidelines, i.e. dietary advice (e.g. small frequent meals, low carbohydrate content, high fiber, balancing carbohydrate intake over the course of the day, three small meals and 2 small snacks rather than one large meal) and exercise. A consultation with a diabetologist is highly recommended. 10. Fasting Serum amylase ≤ 2 × ULN 11. Fasting Serum lipase ≤ ULN Exclusion Criteria: Patients eligible for this Treatment Plan must not meet any of the following criteria: 1. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor. 2. Patient has history of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib. 3. Patient with established diagnosis of diabetes mellitus type I or uncontrolled type II. 4. Patient has a known history of Steven Johnson's syndrome or toxic epidermal necrolysis. 5. Patient has a known history of Human Immunodeficiency Virus (HIV) infection. 6. Patient has had surgery within 14 days prior to starting program drug or has not recovered from major side effects. 7. Patient has not recovered to grade 1 or better (except for alopecia) from related side effects of prior antineoplastic therapies. 8. Patient has other prior or concurrent malignancy, with the exception of adequately treated basal or squamous cell skin cancer or other in situ cancer, or any other cancer from which the patient has been disease-free for ≥ 3 years. 9. Patient has central nervous system (CNS) involvement, except for patients fulfilling the following 3 criteria: - completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of program treatment and - CNS tumor is clinically stable at the start of program treatment and - patient is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases 10. 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). 10)Patient who has other concurrent severe and/or uncontrolled medical conditions that would, in the Treating Physician's judgment, contraindicate administration of alpelisib (e.g. active or uncontrolled severe infection, chronic active hepatitis, immunocompromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrolment, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, etc.). 11)Patient who is concurrently being treated with drugs known to be strong inhibitors or inducers of the isoenzyme CYP3A; switching to different medications prior to start of program treatment is allowed within the last 5 days prior to starting program treatment. 12)Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to start of program treatment, or who have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular). 13) Patient is pregnant or lactating, where pregnancy is defined as state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) lab test.

Eligibility Gender
Eligibility Age
Minimum: 18 Years~Maximum: 99 Years

Novartis Pharmaceuticals

Novartis Pharmaceuticals

Novartis Pharmaceuticals
NCT Number
hormone receptor positive
breast cancer
PIK3CA mutation
MeSH Terms
Breast Neoplasms