ALPINIST: Study to Assess the Safety of Alpelisib Plus Fulvestrant, in Men and Post-menopausal Women With HR-positive, HER2-negative, Advanced Breast Cancer (aBC) With PIK3CA Mutation, Whose Disease Progressed on or After Endocrine Treatment

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05631795

Collaborator

(none)

100

Enrollment

Location

Arm

27.2

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety of alpelisib plus fulvestrant in men and post-menopausal women with HR-positive, HER2-negative, advanced or metastatic breast cancer (aBC) with a PIK3CA mutation, whose disease has progressed on or after endocrine-based treatment

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer	Drug: Alpelisib Drug: Fulvestrant	Phase 4

Detailed Description

This is a Phase IV, prospective, multicenter, open-label, non-comparative interventional study to assess the safety of alpelisib plus fulvestrant in men and post-menopausal women with HR-positive, HER2-negative, aBC with a PIK3CA mutation, whose disease has progressed on or after endocrine-based treatment.

Participants will be treated with alpelisib 300 mg orally once daily starting on Cycle 1 Day 1 in combination with fulvestrant (intramuscular injection) 500 mg on Cycle 1 Day 1 and Day 15, and Day 1 of every cycle thereafter in a 28 day cycle. Patients may be discontinued from treatment earlier due to unacceptable toxicity, disease progression, withdrawal of consent, or at the discretion of the investigator or the patient.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ALPelisib INdia Safety STudy (ALPINIST): A Phase IV, Prospective, Multicenter, Open-label, Non-comparative, Interventional Study to Assess the Safety of Alpelisib Plus Fulvestrant, in Men and Post-menopausal Women With HR Positive, HER2-negative, Advanced Breast Cancer (aBC) With a PIK3CA Mutation, Whose Disease Has Progressed on or After Endocrine Based Treatment.

Actual Study Start Date :

Aug 10, 2022

Anticipated Primary Completion Date :

Nov 15, 2024

Anticipated Study Completion Date :

Nov 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alpelisib + fulvestrant Alpelisib 300 mg orally once daily starting on Cycle 1 Day 1 in combination with fulvestrant (intramuscular injection) 500 mg on Cycle 1 Day 1 and Day 15, and Day 1 of every cycle thereafter in a 28 day cycle.	Drug: Alpelisib Film coated tablet for oral use. Participants will be treated with 300 mg of alpelisib once daily starting on Cycle 1 Day 1 Drug: Fulvestrant Injection for intramuscular administration. Participants will be treated with fulvestrant 500 mg on Cycle 1 Day 1 and Day 15, and Day 1 of every cycle thereafter in a 28-day cycle.

Arm

Intervention/Treatment

Experimental: Alpelisib + fulvestrant

Alpelisib 300 mg orally once daily starting on Cycle 1 Day 1 in combination with fulvestrant (intramuscular injection) 500 mg on Cycle 1 Day 1 and Day 15, and Day 1 of every cycle thereafter in a 28 day cycle.

Drug: Alpelisib

Film coated tablet for oral use. Participants will be treated with 300 mg of alpelisib once daily starting on Cycle 1 Day 1

Drug: Fulvestrant

Injection for intramuscular administration. Participants will be treated with fulvestrant 500 mg on Cycle 1 Day 1 and Day 15, and Day 1 of every cycle thereafter in a 28-day cycle.

Outcome Measures

Primary Outcome Measures

Percentage of participants with at least one on-treatment adverse events (AEs) [From start of treatment up to 30 days after last dose of study treatment, assessed up to approximately 7 months]
Percentage of participants with at least one on-treatment AEs. An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease) in a participant. On-treatment period is defined as up to 30 days after last dose of study drug

Secondary Outcome Measures

Percentage of participants with Serious AEs (SAEs) [From start of treatment up to 30 days after last dose of study treatment, assessed up to approximately 7 months]
Percentage of participants with SAEs. An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or is an abnormal pregnancy outcome
Percentage of participants with Adverse Drug Reactions (ADRs) [From start of treatment up to 30 days after last dose of study treatment, assessed up to approximately 7 months]
Percentage of participants with ADRs. An ADR is defined as AEs that are, in the investigator's opinion, of causal relationship to the study treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Participants with confirmed PIK3CA mutant advanced or metastatic breast cancer
Postmenopausal females and males ≥ 18 years old with confirmed HR-positive, HER2-negative advanced or metastatic breast cancer.
Adequate liver function
Adequate renal function
Fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4%
ECOG (Eastern Cooperative Oncology Group) Performance Status < 2
Fasting Serum amylase ≤ 2 × ULN and Fasting Serum lipase ≤ ULN
Potassium within normal limits, or corrected with supplements
Calcium (corrected for serum albumin) and magnesium within normal limits or ≤ grade 1 if judged clinically not significant by the investigator

Key Exclusion Criteria:

Known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant
Participant ineligible for endocrine therapy per the investigator's judgment
Participant has received prior treatment with any PI3K inhibitors and / or mTOR inhibitor
Participant with type I diabetes or not controlled type II (based on FPG and HbA1c, see inclusion criterion 6)
Participant 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-melanomatous skin cancer or curatively resected cervical cancer
Participant has not recovered to grade 1 or better from related side effects of prior anti cancer therapy (with the exception of alopecia)
Participants receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except in cases outlined below: Topical applications, inhaled sprays, eye drops or local injections are allowed. Participants on stable low dose of corticosteroids for at least two weeks prior to enrollment are allowed
Bilateral diffuse lymphangitic carcinomatosis
Participants with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required
Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is ≤2.0)
Any severe and/ or uncontrolled medical conditions
Participant with severe liver impairment (Child Pugh score B/C)
Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study
Participant has documented pneumonitis/interstitial lung disease which is active and requiring treatment
Participant has active cardiac disease or a history of cardiac dysfunction
Participants with unresolved osteonecrosis of the jaw
Participant has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
Participant is a nursing (lactating) or pregnant woman
Participant is a woman of child-bearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and at least for 1 week (for alpelisib) or 1 year (for fulvestrant based on prescribing label) after the last dose of each study drug (whichever comes later).
Participant is a sexually active male unwilling to use a condom during intercourse while taking study treatment, and for 1 week (for alpelisib) or 1 year (for fulvestrant based on prescribing label) after stopping each study drug (whichever comes later). A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm during study and up to the time period specified above.