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

NCT05631795 | Completed Phase 4

• 1 other identifier: CBYL719CIN01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 12

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

Conditions

Advanced Breast Cancer

Keywords

HR+; HER2-negative; PI3K; CDK4/6 inhibitor; ER+; PgR+; men; postmenopausal; aromatase inhibitor

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with at least one on-treatment adverse events (AEs)

  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

  From start of treatment up to 30 days after last dose of study treatment, assessed up to approximately 7 months

Secondary Outcomes (2)

• 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 Adverse Drug Reactions (ADRs)

  From start of treatment up to 30 days after last dose of study treatment, assessed up to approximately 7 months

Study Arms (1)

Alpelisib + fulvestrant

EXPERIMENTAL

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; Drug: Fulvestrant

Interventions

Alpelisib DRUG

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

Alpelisib + fulvestrant

Fulvestrant DRUG

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.

Alpelisib + fulvestrant

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Guwahati, Assam, 781016, India

Location

Novartis Investigative Site

Surat, Gujarat, 395009, India

Location

Novartis Investigative Site

Thalassery, Kerala, 670103, India

Location

Novartis Investigative Site

Trivandrum, Kerala, 695 011, India

Location

Novartis Investigative Site

Bhopal, Madhya Pradesh, 462001, India

Location

Novartis Investigative Site

Mumbai, Maharashtra, 400 012, India

Location

Novartis Investigative Site

Nagpur, Maharashtra, 440001, India

Location

Novartis Investigative Site

Pune, Maharashtra, 411040, India

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Novartis Investigative Site

Hyderabad, Telangana, 500004, India

Location

Novartis Investigative Site

Ahmedabad, 380016, India

Location

Novartis Investigative Site

Kolkata, 700026, India

Location

MeSH Terms

Conditions

Multiple Endocrine Neoplasia Type 1

Interventions

Alpelisib; Fulvestrant

Condition Hierarchy (Ancestors)

Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: November 30, 2022
• Study Start: August 9, 2022
• Primary Completion: June 12, 2025
• Study Completion: June 12, 2025
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

IN (12)