ALPELISIB for Hormone receptor-positive, HER2-negative metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- 1. Patient is an adult male or female (≥ 18 years of age) with advanced (loco regionally 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. Written informed consent 4. If female, then the patient is postmenopausal. Postmenopausal status is defined either by: - Prior bilateral oophorectomy - Age ≥60 - Age <60 and amenorrhea for ≥12 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 evidence of recurrence or progression during or after AI therapy (i.e. letrozole, anastrozole, exemestane) or AI and CDK 4/6i therapy (ribociclib, palbociclib, abemaciclib). AI therapy does not need to be the latest treatment regimen. 6. Patient has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory. 7. Patient has adequate bone marrow and organ function as defined by the following laboratory values: 1) Absolute neutrophil count ≥ 1.5 × 109/L 2) Platelets ≥ 100 × 109/L 3) Hemoglobin ≥ 9.0 g/dL 4) Potassium, magnesium and calcium (corrected for serum albumin) within normal limits or ≤ grade 1 according to National Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 if judged clinically not significant by the Treating Physician, or corrected with supplements 5) INR ≤ 1.5 6) Creatinine clearance > 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) 10) Fasting Serum Amylase ≤ 2 × ULN 11) Fasting Serum Lipase ≤ ULN"}

Exclusion criteria

• {"criterion_text":"- 1) Patient has history of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib. 2) Patient with established diagnosis of diabetes mellitus type I or uncontrolled type II. 3) Patient has a known history of Steven Johnson’s syndrome or toxic epidermal necrolysis. 4) Patient has a known history of Human Immunodeficiency Virus (HIV) infection. 5) Patient has had surgery within 14 days prior to starting program drug or has not recovered from major adverse reactions. 6) Patient has not recovered to grade 1 or better (except for alopecia) from related adverse reactions of prior antineoplastic therapies. 7) 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. 8) 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 9) 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 adverse reactions 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) Male patient who does not apply highly effective contraception during the treatment with alpelisib and through the duration as defined below after the final dose of alpelisib. - Sexually active males should use a condom during intercourse while taking drug and for at least 4 weeks after stopping alpelisib and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid."}

Primary endpoints

• {"endpoint_text":"- Exposure-adjusted incidence rate of grade 3 or 4 hyperglycemia within the first 3 months or 30 days after the treatment discontinuation whichever comes first","definition_or_measurement_approach":"Measured as exposure-adjusted incidence rate of grade 3 or 4 hyperglycemia within the first 3 months or within 30 days after treatment discontinuation, whichever comes first."}

Secondary endpoints

• {"endpoint_text":"- 1) Median time to the first grade 3 or 4 hyperglycemia from the first dose of study treatment until 30 days from permanent treatment discontinuation","definition_or_measurement_approach":"Time from first dose to first occurrence of grade 3 or 4 hyperglycemia, censored at 30 days after permanent treatment discontinuation."}
• {"endpoint_text":"- 2) Exposure-adjusted incidence rate of any grade hyperglycemia within the first 3 months or 30 days after the treatment discontinuation whichever comes first","definition_or_measurement_approach":"Exposure-adjusted incidence rate of any grade hyperglycemia within first 3 months or within 30 days after treatment discontinuation, whichever comes first."}
• {"endpoint_text":"- 3) ORR from randomization to 30 days after the treatment discontinuation PFS from randomization to the end of the study","definition_or_measurement_approach":"ORR (objective response rate) measured from randomization until 30 days after treatment discontinuation; PFS (progression-free survival) measured from randomization to end of study."}
• {"endpoint_text":"- 4) Exposure-adjusted incidence rate of all grade hyperglycemia,","definition_or_measurement_approach":"Exposure-adjusted incidence rate of all-grade hyperglycemia (measurement period not further specified beyond text)."}

Croatia

Earliest CTIS Part Ii Submission Date

10-02-2025

Latest Decision Or Authorization Date

27-02-2025

Processing Time Days

17

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Croatian Cooperative Group For Clinical Trial Research In Oncology

Organisation Type

Patient organisation/association

Country Of Registered Address

Croatia

Third parties

• {"country":"Croatia","full_name":"Croatian Cooperative Group For Clinical Trial Research In Oncology","duties_or_roles":"codes: 11,5,6","organisation_type":"Patient organisation/association"}