What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving PI3K inhibitors like Alpelisib, often include targeted therapies and endocrine therapies. Known side effects of Alpelisib include hyperglycemia, rash, diarrhea, and liver function abnormalities. Other common treatments such as aromatase inhibitors can lead to bone density loss, fractures, and cardiovascular risks. Tamoxifen, another endocrine therapy, may cause hot flashes, increased risk of thromboembolic events, and endometrial cancer. Chemotherapy, often used in more aggressive cases, can result in nausea, fatigue, hair loss, and increased risk of infections.

What prior FDA approvals exist?

The FDA has approved the PI3K inhibitor alpelisib for use in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer. This approval was based on a phase III trial demonstrating its efficacy in this patient population. Other treatments for breast cancer include hormone therapies, chemotherapy, and targeted therapies such as trastuzumab and pertuzumab for HER2-positive breast cancer. These treatments are tailored based on the specific characteristics of the tumor, such as hormone receptor status and HER2 expression.

What other types of research exist?

Promising alternatives to Alpelisib for breast cancer patients include: 1) Trastuzumab Deruxtecan (Enhertu), an antibody-drug conjugate targeting HER2-positive breast cancer. 2) Sacituzumab Govitecan (Trodelvy), an antibody-drug conjugate for triple-negative breast cancer. 3) Tucatinib (Tukysa), a HER2-targeted tyrosine kinase inhibitor. 4) Pembrolizumab (Keytruda), an immune checkpoint inhibitor for PD-L1 positive breast cancer. 5) Ribociclib (Kisqali) and Abemaciclib (Verzenio), CDK4/6 inhibitors for HR-positive, HER2-negative breast cancer.

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Alpelisib + Trastuzumab + Pertuzumab for Breast Cancer (EPIK-B2 Trial)

Phase 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery or is metastatic)

Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Must not have

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)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 70 months

Awards & highlights

Pivotal Trial

Summary

This trial tested a combination of drugs for patients with advanced breast cancer that has a specific genetic mutation. The goal was to see if this combination could better control the cancer by blocking growth signals. The study was stopped due to changes in treatment approaches, not because of safety issues.

Who is the study for?

This trial is for HER2-positive advanced breast cancer patients with a PIK3CA mutation who completed up to 8 cycles of taxane-based therapy. They must have good performance status and organ function, no inflammatory breast cancer, uncontrolled heart issues, history of severe skin reactions or lung disease, diabetes type I or uncontrolled type II.

What is being tested?

The study tests the effectiveness and safety of Alpelisib in combination with Trastuzumab and Pertuzumab as maintenance therapy post-taxane induction. It's a two-part study: an initial phase to confirm safe dosage followed by a randomized comparison with placebo.

What are the potential side effects?

Alpelisib may cause high blood sugar levels, rash, diarrhea, nausea; Trastuzumab can lead to heart problems or allergic reactions; Pertuzumab might cause diarrhea, hair loss or fatigue. Side effects vary among individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is HER2-positive and cannot be removed by surgery or has spread.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with inflammatory breast cancer.

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My cancer got worse during the initial treatment before starting alpelisib.

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I have been diagnosed with type I diabetes or my type II diabetes is not under control.

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I have had acute pancreatitis within the last year or a history of chronic pancreatitis.

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I have serious heart problems that are not under control.

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I have been diagnosed with pneumonitis or interstitial lung disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 70 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 70 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 70 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1: Incidence of dose limiting toxicities (DLTs) for each dose level

Part 2: Progression Free Survival (PFS)

Secondary study objectives

Part 1: Alpelisib concentrations by timepoint and dose level

Part 2: Change in Functional Assessment of Cancer Therapy - Breast (FACT-B) treatment outcomes index (TOI) from baseline

Part 2: Clinical Benefit Rate (CBR) with confirmed response

+8 more

Side effects data

From 2023 Phase 3 trial • 572 Patients • NCT02437318

62%

Hyperglycaemia

57%

Diarrhoea

45%

Nausea

35%

Rash

35%

Decreased appetite

26%

Vomiting

26%

Weight decreased

24%

Fatigue

24%

Stomatitis

20%

Asthenia

20%

Alopecia

18%

Mucosal inflammation

18%

Pruritus

17%

Dysgeusia

17%

Headache

15%

Dry skin

14%

Oedema peripheral

14%

Pyrexia

14%

Back pain

13%

Rash maculo-papular

11%

Dyspepsia

11%

Abdominal pain

11%

Arthralgia

10%

Dry mouth

10%

Urinary tract infection

10%

Blood creatinine increased

10%

Gamma-glutamyltransferase increased

10%

Aspartate aminotransferase increased

10%

Cough

Nasopharyngitis

Pain in extremity

Dizziness

Hypertension

Anaemia

Constipation

Alanine aminotransferase increased

Hypokalaemia

Dyspnoea

Myalgia

Muscle spasms

Insomnia

Lipase increased

Abdominal pain upper

Lymphoedema

Musculoskeletal pain

Erythema

Upper respiratory tract infection

Bone pain

Hot flush

Osteonecrosis of jaw

Acute kidney injury

Pneumonitis

Pulmonary embolism

Dehydration

Upper gastrointestinal haemorrhage

General physical health deterioration

Cellulitis

Pleural effusion

Hypersensitivity

Pneumonia

Hyponatraemia

Muscular weakness

Brain oedema

Renal failure

Erythema multiforme

100%

80%

60%

40%

20%

Study treatment Arm

Placebo qd + Fulvestrant

Alpelisib qd + Fulvestrant

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Part 2: Alpelisib + Trastuzumab + PertuzumabExperimental Treatment3 Interventions

Trastuzumab (6mg/kg) + pertuzumab (420 mg) in combination with 200mg alpelisib, with potential for intra-participant dose escalation to 250 mg

Group II: Part 1: Alpelisib + Trastuzumab + PertuzumabExperimental Treatment3 Interventions

In the Part 1, up to 3 alpelisib dose levels may be sequentially tested in 3 cohorts of subjects: Cohort A: Alpelisib 300mg + trastuzumab (6mg/kg) + pertuzumab (420 mg) Cohort B: Alpelisib 250 mg+ trastuzumab (6mg/kg) + pertuzumab (420 mg) Cohort C: Alpelisib 200mg + trastuzumab (6mg/kg) + pertuzumab (420 mg)

Group III: Part 2: Alpelisib matching Placebo + Trastuzumab + PertuzumabPlacebo Group3 Interventions

Trastuzumab (6mg/kg) + pertuzumab (420 mg) in combination with 200 mg alpelisib matching placebo, with potential for intra-participant dose escalation to 250 mg

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alpelisib

2018

Completed Phase 3

~960

Trastuzumab

2014

Completed Phase 4

~5190

Pertuzumab

2014

Completed Phase 3

~7500

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for breast cancer include targeted therapies and endocrine treatments. PI3K inhibitors like Alpelisib target the phosphoinositide 3-kinase (PI3K) pathway, which is often mutated in breast cancer, leading to uncontrolled cell growth. By inhibiting this pathway, Alpelisib can reduce tumor growth and proliferation. Endocrine therapies, such as aromatase inhibitors and selective estrogen receptor modulators (SERMs), work by blocking the effects of estrogen, a hormone that can promote the growth of hormone receptor-positive breast cancer cells. These treatments are crucial as they offer more personalized and effective options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.