EPIK-B2: A Two Part, Phase III, Multicenter, Randomized (1:1), Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation
EPIK-B2: Alpelisib for HER2+ Breast Cancer
Plain English Summary
Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation is a Phase 3 clinical trial sponsored by Novartis Pharmaceuticals studying Advanced HER2+Breast Cancer. Tests alpelisib with trastuzumab and pertuzumab for HER2-positive advanced breast cancer with PIK3CA mutation. For patients with advanced HER2+ breast cancer who have completed induction therapy. Participation involves taking alpelisib or placebo daily and regular check-ups. Alternative treatments include standard chemotherapy and targeted therapies. The trial aims to enroll 19 participants.
Official Summary
The purpose of this two part multicenter, randomized, double-blind, placebo-controlled, Phase III study is to evaluate the efficacy and safety of alpelisib compared to alpelisib matching-placebo in combination with trastuzumab and pertuzumab as maintenance treatment of patients with HER2-positive advanced breast cancer whose tumor harbors a PIK3CA mutation following induction therapy with a taxane in combination with trastuzumab and pertuzumab. Part 1 is the open-label, safety run-in part of the study, designed to confirm the recommended phase 3 dose (RP3D) dose of alpelisib in combination with trastuzumab and pertuzumab. Following Part 1, Part 2 will be initiated, which is the randomized, Phase III part of the study.
Who Can Participate
Here is what you need to know about eligibility for this trial. Eligible if HER2-positive breast cancer, advanced stage, completed induction therapy, and has PIK3CA mutation. Not eligible if has inflammatory breast cancer, disease progression, diabetes, heart disease, or certain lung conditions. This trial is studying Advanced HER2+Breast Cancer, so participants generally need a confirmed diagnosis.
What They're Measuring
Measures include progression-free survival and overall response rate, beneficial for patients by potentially extending treatment duration. The specific primary outcome measures are: Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level (6 weeks); Part 2: Progression Free Survival (PFS) (Up to approximately 38 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.
Why This Trial Matters
This trial aims to fill a treatment gap for HER2+ breast cancer patients with PIK3CA mutations, offering a new combination therapy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Advanced HER2+Breast Cancer, where improved treatment options are needed.
Investor Insight
Market size is large for HER2+ breast cancer, with strong competition but a promising landscape for innovative treatments. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.
Is This Trial Right for Me?
Ask your doctor if you have advanced HER2+ breast cancer and a PIK3CA mutation. Participation involves daily medication and regular clinic visits. The trial is being conducted at 11 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: RANDOMIZED
- Model: SEQUENTIAL
- Masking: QUADRUPLE
- Enrollment: 19 participants
Interventions
- DRUG: Alpelisib — Alpelisib orally taken - continuous once daily, in a 21-day cycle.
- DRUG: Alpelisib matching Placebo — Alpelisib matching placebo orally taken - continuous once daily, in a 21-day cycle
- DRUG: Trastuzumab — Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)
- DRUG: Pertuzumab — Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)
Primary Outcomes
- Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level (6 weeks)
- Part 2: Progression Free Survival (PFS) (Up to approximately 38 months)
Secondary Outcomes
- Part 1: Alpelisib concentrations by timepoint and dose level (Day 8 of Cycle 1 and then Day 1 of Cycle 2, Cycle 4, Cycle 6 and Cycle 10 (Cycle = 21 days))
- Part 2: Overall survival (OS) (Key Secondary) (Up to approximately 70 months)
- Part 2: Summary statistics of alpelisib concentrations by timepoint and dose level (Day 8 of Cycle 1 and then Day 1 of Cycle 2, Cycle 4, Cycle 6 and Cycle 10 (Cycle = 21 days))
- Part 2: Overall response rate (ORR) with confirmed response (Up to approximately 38 months)
- Part 2: Clinical Benefit Rate (CBR) with confirmed response (Up to approximately 38 months)
Full Eligibility Criteria
Inclusion Criteria: * Participant has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery or is metastatic). * Participant has received pre-study induction therapy with up to and including a maximum of 8 cycles of a taxane (docetaxel, paclitaxel, or nab-paclitaxel), plus trastuzumab and pertuzumab. 4 or 5 cycles of induction therapy are permitted if discontinuation of taxane was due to taxane toxicity. Of note, participants enrolled in Part 1 of this study received 4-6 cycles of pre-study induction therapy. * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Participant has adequate bone marrow and organ function * Applies only to Part 2: Participant has a PIK3CA mutation(s) present in tumor prior to enrollment, locally confirmed per test listed in protocol or as determined by a Novartis designated central laboratory. Exclusion Criteria: * Participant with inflammatory breast cancer at screening. * Participant with evidence of disease progression during the pre-study induction therapy and prior to first dose of alpelisib (or alpelisib/alpelisib matching-placebo for Part 2) * Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose (FPG) and HbA1c. * Participant has a known history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis * Participant has clinically significant, uncontrolled heart disease and/or recent cardiac events * Participant has a history of Steven-Johnson Syndrome (SJS), erythema multiforme (EM) or Toxic Epidermal Necrolysis (TEN). * Participant has currently documented pneumonitis/interstitial lung disease Other protocol-defined Inclusion/Exclusion may apply.
Trial Locations
- Highlands Oncology Group, Fayetteville, Arkansas, United States
- University of California LA, Los Angeles, California, United States
- Novartis Investigative Site, Leuven, Belgium
- Novartis Investigative Site, Liège, Belgium
- Novartis Investigative Site, Changchun, Jilin, China
- Novartis Investigative Site, Shanghai, China
- Novartis Investigative Site, Saint-Cloud, Hauts De Seine, France
- Novartis Investigative Site, Saint-Herblain, France
- Novartis Investigative Site, Florence, FI, Italy
- Novartis Investigative Site, Kuala Lumpur, Malaysia
- ...and 1 more locations
Frequently Asked Questions
What is clinical trial NCT04208178?
NCT04208178 is a Phase 3 INTERVENTIONAL study titled "Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation." It is currently active, not recruiting and is sponsored by Novartis Pharmaceuticals. The trial targets enrollment of 19 participants.
What conditions does NCT04208178 study?
This trial investigates treatments for Advanced HER2+Breast Cancer. The primary condition under study is Advanced HER2+Breast Cancer.
What treatments are being tested in NCT04208178?
The interventions being studied include: Alpelisib (DRUG), Alpelisib matching Placebo (DRUG), Trastuzumab (DRUG), Pertuzumab (DRUG). Alpelisib orally taken - continuous once daily, in a 21-day cycle.
What does Phase 3 mean for NCT04208178?
Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.
What is the current status of NCT04208178?
This trial is currently "Active, Not Recruiting." It started on 2020-07-16. The estimated completion date is 2027-02-26.
Who is sponsoring NCT04208178?
NCT04208178 is sponsored by Novartis Pharmaceuticals. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT04208178?
The trial aims to enroll 19 participants. The trial status is active, not recruiting.
How is NCT04208178 designed?
This is a interventional study, uses randomized allocation, follows a sequential design, employs quadruple masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.
What are the primary outcomes being measured in NCT04208178?
The primary outcome measures are: Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level (6 weeks); Part 2: Progression Free Survival (PFS) (Up to approximately 38 months). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT04208178 being conducted?
This trial is being conducted at 11 sites, including Fayetteville, Arkansas; Los Angeles, California; Leuven; Liège and 7 more sites (United States, Belgium, China).
Where can I find official information about NCT04208178?
The official record for NCT04208178 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT04208178. This government database provides the most up-to-date and detailed information about the trial.
What is NCT04208178 testing in simple terms?
Tests alpelisib with trastuzumab and pertuzumab for HER2-positive advanced breast cancer with PIK3CA mutation. For patients with advanced HER2+ breast cancer who have completed induction therapy.
Why is this trial significant?
This trial aims to fill a treatment gap for HER2+ breast cancer patients with PIK3CA mutations, offering a new combination therapy. As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.
What are the potential risks of participating in NCT04208178?
Key risks include potential side effects like skin rashes, diarrhea, and high blood sugar. Monitor for any unusual symptoms and report them to your healthcare provider. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT04208178?
Ask your doctor if you have advanced HER2+ breast cancer and a PIK3CA mutation. Participation involves daily medication and regular clinic visits. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT04208178 signal from an investment perspective?
Market size is large for HER2+ breast cancer, with strong competition but a promising landscape for innovative treatments. This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.
What happens if the treatment in this trial doesn't work?
Participation involves taking alpelisib or placebo daily and regular check-ups. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
Related Conditions
More Advanced HER2+Breast Cancer Trials
This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.