Evaluating PIK3CA mutations and the effectiveness of alpelisib in advanced breast cancer

A Descriptive Study of PIK3CA Mutations and Outcomes With Alpelisib in Patients With HR-positive and HER2-negative Advanced Breast Cancer (ABC)/ Metastatic Breast Cancer (MBC) in India

This study is testing how common PIK3CA mutations are in women with advanced breast cancer and whether a new treatment combining alpelisib and fulvestrant can help those with the mutation feel better.

Quick facts

• Study type: Observational
• Enrollment: 200 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Novartis (industry)
• Locations: 8 sites (New Delhi, Delhi and 7 other locations)
• Trial ID: NCT05022342 on ClinicalTrials.gov

What this trial studies

This observational study aims to assess the prevalence of PIK3CA mutations in patients with hormone receptor-positive and HER2-negative advanced or metastatic breast cancer in India. It consists of two parts: Part A focuses on determining the proportion of PIK3CA mutation-positive patients, while Part B evaluates the effectiveness and tolerability of alpelisib combined with fulvestrant in those patients. The study will enroll approximately 1200 patients for Part A and 200 for Part B, with data collected from routine clinical practice without any investigational interventions. Patient consent is required for participation, and their mutation status will be tested at a central laboratory.

Who should consider this trial

Good fit: Ideal candidates include males and females (post-menopausal or pre-menopausal with ovarian ablation) diagnosed with hormone receptor-positive and HER2-negative advanced or metastatic breast cancer.

Not a fit: Patients with breast cancer that is not hormone receptor-positive or HER2-negative, or those without PIK3CA mutations, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the effectiveness of targeted therapy for patients with PIK3CA mutations in advanced breast cancer.

How similar studies have performed: Other studies have shown promising results with similar approaches in targeting PIK3CA mutations, indicating potential for success in this study.

Eligibility criteria

Inclusion Criteria:

PART A:

1. Males (≥18 years of age), post-menopausal\* females or pre-menopausal\*\* females with ovarian ablation (as per physician decision).
2. Patients with confirmed diagnosis of ABC/MBC (locoregionally recurrent not amenable to curative therapy or metastatic)
3. Patient with histologically and/or cytologically confirmed diagnosis of HR-positive (ER+ and/or PgR+), as well as HER2-negative breast cancer by local laboratory (HER2- by Immunohistochemistry \[IHC\], for borderline2+ Fluorescence In Situ Hybridization \[FISH\])
4. A separate signed patient ICF for Part A of the study must be obtained prior to any data collection and sample shipment to the central designated laboratory
5. Patient's tumor tissue (archival or fresh) is available to be sent to a central laboratory for PIK3CA testing. In case, tissue sample (archival or fresh) is not available or feasible, liquid biopsy may be allowed.

PART B:

1. Males (≥18 years of age), post-menopausal\* females or pre-menopausal\*\* females with ovarian ablation (as per physician decision).
2. Patients with confirmed diagnosis of ABC/MBC (locoregionally recurrent not amenable to curative therapy or metastatic) - for direct enrollment patients into Part B of the study.
3. Patient with histologically and/or cytologically confirmed diagnosis of HR-positive (ER+ and/or PgR+), as well as HER2-negative breast cancer by local laboratory (HER2- by Immunohistochemistry \[IHC\], for borderline2+ Fluorescence In Situ Hybridization \[FISH\]) - for direct enrollment patients into Part B of the study.
4. Participants with confirmed positive PIK3CA mutation status prior to study entry.
5. A separate signed ICF for Part B of the study must be obtained by all the patients, prior to any data collection, irrespective of patients who are being enrolled from Part A of the study or who are being enrolled directly into Part B of the study.
6. Physician decision to treat patients with alpelisib plus fulvestrant, according to the prescribing label and the local practicing guidelines.
7. Patient should be alpelisib treatment naïve.

Exclusion Criteria:

PART A:

1. Prior or current enrollment in any interventional clinical trial for ABC/MBC.

Part

PART B:

1. Patients' who had prior or current exposure to alpelisib or had prior or current exposure to any other PIK3CA inhibitor should be excluded.
2. Known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant.
3. Participant with type I or uncontrolled type II diabetes mellitus (HbA1c \>7, \[as per ADA/ACP guidelines 2020\]).
4. 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).
5. Participant has documented pneumonitis/interstitial lung disease which is active and requiring treatment.
6. Participant with unresolved osteonecrosis of the jaw.
7. Participant reports history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis, major surgery, any relevant medical condition, gastrointestinal (GI) condition preventing absorption, Child Pugh score B or C etc.

Where this trial is running

New Delhi, Delhi and 7 other locations

• Novartis Investigative Site — New Delhi, Delhi, India (RECRUITING)
• Novartis Investigative Site — Mumbai, Maharashtra, India (RECRUITING)
• Novartis Investigative Site — Pune, Maharashtra, India (RECRUITING)
• Novartis Investigative Site — Bhubaneshwar, Orissa, India (RECRUITING)
• Novartis Investigative Site — Chandigarh, Punjab, India (RECRUITING)
• Novartis Investigative Site — Kolkata, West Bengal, India (RECRUITING)
• Novartis Investigative Site — Bhubaneswar, India (RECRUITING)
• Novartis Investigative Site — Kolkata, India (RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Breast Cancer, advanced breast cancer, metastatic breast cancer, PIK3CA mutations