What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving PI3K inhibitors like Alpelisib, often include chemotherapy, hormone therapy, and targeted therapy. The side effects of these treatments can vary but generally include hyperglycemia, gastrointestinal issues (such as diarrhea and nausea), fatigue, and skin rashes. Specific to Alpelisib, patients may experience hyperglycemia, rash, diarrhea, and liver function abnormalities. Other common side effects of breast cancer treatments can include alopecia, neuropathy, and bone density loss, particularly with the use of aromatase inhibitors.

What prior FDA approvals exist?

Alpelisib, a PI3K inhibitor, has been approved by the FDA for use in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer. This approval is based on its ability to target the PI3K pathway, which is often mutated in breast cancer. Other related drugs include everolimus, an mTOR inhibitor, which has shown efficacy when combined with hormone therapy in similar patient populations. These targeted therapies represent a significant advancement in the treatment of specific subtypes of breast cancer by addressing underlying genetic mutations.

What other types of research exist?

Promising novel alternatives to Alpelisib for breast cancer patients in 2024 include: 1) Piqray (Alpelisib) combined with other targeted therapies such as CDK4/6 inhibitors (e.g., Ribociclib, Palbociclib) for enhanced efficacy. 2) AKT inhibitors like Capivasertib, which target the same PI3K/AKT/mTOR pathway. 3) PARP inhibitors (e.g., Olaparib, Talazoparib) for patients with BRCA mutations. 4) Immunotherapy agents such as Pembrolizumab for triple-negative breast cancer. 5) Antibody-drug conjugates like Trastuzumab Deruxtecan for HER2-positive breast cancer.

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iNOS Inhibitor

Combination Therapy for Advanced Breast Cancer

Q: What is the mechanism of action of this treatment?

Breast cancer treatments often target specific pathways involved in cancer cell growth and survival. Alpelisib, a PI3K inhibitor, works by blocking the PI3K/AKT/mTOR pathway, which is frequently activated in breast cancer, particularly in tumors with PIK3CA mutations. This inhibition can reduce cancer cell proliferation and induce apoptosis. Other common treatments include hormone therapies like aromatase inhibitors, which lower estrogen levels to slow the growth of hormone receptor-positive cancers, and HER2-targeted therapies like trastuzumab, which block the HER2 receptor to prevent cell growth in HER2-positive cancers. Understanding these mechanisms is crucial for personalizing treatment plans, improving efficacy, and minimizing side effects for breast cancer patients.

Phase 2

Recruiting

Led By Polly A Niravath, MD

Research Sponsored by The Methodist Hospital Research Institute

Eligibility Criteria Checklist

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

Must have

Histologically confirmed HER2 negative MpBC and/or Triple Negative Breast Cancer (TNBC) with squamous and/or sarcomatoid elements, including osseous, chondroid, and spindle morphology

Adequate organ and marrow function as defined below: Hemoglobin ≥9.0 g/dl, Absolute neutrophil count ≥1000/μL, Platelet count ≥100,000/μL, Serum total bilirubin (TB) ≤1.5 x institutional upper limit of normal, Aspartate transaminase/alanine transaminase ≤5 x institutional ULN, Creatinine ≤1.5X the ULN or measured creatinine clearance ≥ 60 mL/min/1, Fasting blood glucose of ≤140 mg/dl and HgbA1c ≤7.0

Must not have

Pneumonitis/ interstitial lung disease on baseline CT scan of the chest or moderate to severe chronic lung disease

≥ Grade 2 sensory neuropathy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up the rp2d will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 dlts (study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of an oral cancer drug, an IV chemotherapy drug, and another IV drug in patients with a rare, hard-to-treat type of breast cancer. The goal is to improve treatment response by blocking cancer growth signals and resistance pathways. The study targets patients whose cancer has not responded to other treatments.

Who is the study for?

This trial is for adults with HER2 negative metastatic or advanced metaplastic breast cancer that hasn't improved after previous treatments. Participants must be able to follow the study plan, have measurable disease, and acceptable organ function. Women of childbearing age and sexually active men must use contraception. Exclusions include certain drug interactions, uncontrolled hypertension, serious heart conditions, other active cancers, severe lung disease or neuropathy, pancreatitis, blood clotting disorders on specific anticoagulants, history of severe skin reactions or untreated brain metastases.

What is being tested?

The study tests the combination of alpelisib (taken orally), L-NMMA (given intravenously), and nab-paclitaxel chemotherapy in patients with a specific type of breast cancer. Treatments are given every three weeks until disease progression or unacceptable side effects occur.

What are the potential side effects?

Potential side effects may include digestive issues like nausea and diarrhea from alpelisib; allergic reactions to nab-paclitaxel; fatigue; changes in blood sugar levels; increased risk of infections due to lowered white blood cell counts; nerve damage causing numbness or pain.

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 negative with specific cell types.

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Your blood, liver, and kidney function tests should be within normal range and your blood sugar levels should be controlled.

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I am 18 years old or older.

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

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My cancer is not HER2 positive according to the latest guidelines.

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I can swallow pills.

Exclusion Criteria

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

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I do not have severe lung disease or lung scarring.

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I have moderate to severe numbness or pain in my hands or feet.

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I have serious heart problems or had a recent heart attack.

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I am not allergic to nab-paclitaxel, alpelisib, iNOS inhibitors, or aspirin.

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I am taking medications that affect nitrate/nitrite levels.

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I am currently being treated for another cancer.

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I do not have HIV.

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I have pancreatitis.

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I am on blood thinners that are not warfarin or similar.

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I have untreated brain metastases causing symptoms.

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I have issues absorbing nutrients due to past stomach or intestine surgery or disease.

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I have bone death in my jaw.

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I have an untreated stomach ulcer.

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I have type 1 diabetes or my type 2 diabetes is not under control (Hgb A1c >7%).

Select...

I have been treated with specific cancer drugs like nab-paclitaxel or PI3K, AKT, mTOR inhibitors.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ the rp2d will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 dlts (study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~the rp2d will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 dlts (study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion)

This trial's timeline: 3 weeks for screening, Varies for treatment, and the rp2d will be defined as the highest dose administered at which 6 patients complete treatment with experiencing <2 dlts (study completion is an average of 6 cycles, determined by diseases progression, unacceptable toxicity, physician's discretion) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Define recommended phase II dose (RP2D)

Objective response rate (ORR)

Secondary study objectives

Analysis of responses to an iNOS inhibitor and nab-paclitaxel in combination with alpelisib.

OS of patients with HER2 negative metastatic or locally advanced MpBC

PFS of patients with HER2 negative metastatic or locally advanced MpBC

+1 more

Side effects data

From 2017 Phase 4 trial • 44 Patients • NCT01701973

20%

Dizziness and paresthesias during arginine infusion

20%

Abdominal cramping and diarrhea

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Sitagliptin Plus Pegvisomant

Sitagliptin Plus LNMMA

Sitagliptin

Sitagliptin Plus Exendin 9-39

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: iNOS inhibitor and nab-paclitaxel in combination with alpelisib.Experimental Treatment1 Intervention

iNOS inhibitor and nab-paclitaxel in combination with alpelisib in patients with HER2 negative, metastatic or locally advanced MpBC.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

L-NMMA

2010

Completed Phase 4

~420

0 / 21Eligibility 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

Breast cancer treatments often target specific pathways involved in cancer cell growth and survival. Alpelisib, a PI3K inhibitor, works by blocking the PI3K/AKT/mTOR pathway, which is frequently activated in breast cancer, particularly in tumors with PIK3CA mutations. This inhibition can reduce cancer cell proliferation and induce apoptosis. Other common treatments include hormone therapies like aromatase inhibitors, which lower estrogen levels to slow the growth of hormone receptor-positive cancers, and HER2-targeted therapies like trastuzumab, which block the HER2 receptor to prevent cell growth in HER2-positive cancers. Understanding these mechanisms is crucial for personalizing treatment plans, improving efficacy, and minimizing side effects for breast cancer patients.

Therapeutic targeting of platelet-derived growth factor receptors in solid tumors.Promising novel therapies for the treatment of endometrial cancer.Endocrine therapy for early breast cancer.