Nab-paclitaxel + Alpelisib for Triple Negative Breast Cancer

Overseen By Senthilkumar Damodaran

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Diabetes, Metastatic disease, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, nab-paclitaxel (a chemotherapy) and alpelisib (also known as Piqray, a targeted therapy), in treating triple-negative breast cancer that has not responded well to other chemotherapy treatments. Nab-paclitaxel stops tumor cells from growing and spreading, while alpelisib blocks certain enzymes that aid tumor growth. The trial seeks participants with stage I-III triple-negative breast cancer who still have a tumor after undergoing anthracycline-based chemotherapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients using certain strong inhibitors or inducers of the enzyme CYP3A within 5 days before starting the study. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that nab-paclitaxel and alpelisib are likely to be safe for humans?

Research has shown that the combination of alpelisib and nab-paclitaxel is generally well-tolerated by patients. Studies have found that patients with specific genetic changes, such as PIK3CA mutations, responded positively to this treatment. These studies reported no major safety issues. Most patients experienced manageable side effects, suggesting that the treatment is relatively safe for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for triple negative breast cancer?

Researchers are excited about the combination of alpelisib and nab-paclitaxel for triple-negative breast cancer because it offers a novel approach to treatment. Unlike standard chemotherapy options, this combination includes alpelisib, which specifically targets and inhibits the PI3K pathway, a common driver of cancer cell growth in many tumors. Nab-paclitaxel, a nanoparticle formulation of paclitaxel, allows for more efficient delivery of the chemotherapy drug directly to the tumor cells. This targeted approach not only aims to improve the effectiveness of the treatment but also to reduce the side effects typically associated with traditional chemotherapy.

What evidence suggests that nab-paclitaxel and alpelisib could be effective for triple negative breast cancer?

Research has shown that using alpelisib with nab-paclitaxel is promising for treating triple-negative breast cancer, particularly in patients with PIK3CA mutations. In this trial, participants will receive this combination treatment. Studies have found that this drug combination is generally well-tolerated, meaning patients usually do not experience severe side effects. Patients with PIK3CA-mutated tumors have shown positive responses to this treatment. Nab-paclitaxel stops cancer cells from growing and dividing, while alpelisib blocks enzymes that cancer cells need to grow. This combination aims to effectively shrink tumors before surgery. ^{1 2 4 5 6}

Who Is on the Research Team?

Senthilkumar Damodaran

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with triple-negative breast cancer that hasn't responded to anthracycline chemo. They must have specific genetic changes (PIK3CA or PTEN), good organ function, no severe diabetes, and not be pregnant. Contraception is required during the study. People with certain heart conditions, uncontrolled diseases, or a history of non-compliance are excluded.

Inclusion Criteria

My kidney function tests are within normal limits.

I have undergone sterilization.

I use barrier methods like condoms or diaphragms with spermicide for birth control.

Exclusion Criteria

I have not needed IV antibiotics for an infection in the last 2 weeks.

I don't have any neurological conditions that could affect nerve damage assessment.

You are currently using another type of cancer treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alpelisib orally once daily and nab-paclitaxel intravenously over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 cycles.

12 weeks

4 cycles, each with 3 visits (in-person)

Surgery

Patients may undergo surgery to remove the tumor after completion of study treatment.

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up at 30 days and periodically up to 3 years after surgery.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Nab-paclitaxel

Trial Overview The trial tests nab-paclitaxel combined with alpelisib in patients whose cancer didn't shrink after anthracycline chemotherapy. The goal is to see if this combo can reduce tumor size before surgery by blocking enzymes needed for cell growth and stopping tumor cells from dividing or spreading.

How Is the Trial Designed?

Group I: Treatment (alpelisib, nab-paclitaxel) Experimental Treatment 2 Interventions

Patients receive alpelisib PO QD on days 1-21, and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may then undergo surgery to remove the tumor.

Alpelisib is already approved in United States, European Union for the following indications:

Approved in United States as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Approved in European Union as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a phase II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

Nab-paclitaxel, a nanoparticle albumin-bound form of paclitaxel, is the first nanotechnology-based drug approved for cancer treatment, showing significant promise in breast and pancreatic cancers.

This innovative drug not only enhances the effectiveness and reduces the toxicity of traditional treatments but also demonstrates activity in cancers that typically do not respond to standard taxane therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time? Cucinotto, I., Fiorillo, L., Gualtieri, S., et al.[2022]

Nab-paclitaxel, a new formulation of paclitaxel, has shown a good safety and efficacy profile for treating metastatic breast cancer (MBC), although there is limited data on its impact on overall survival.

In combination with gemcitabine, nab-paclitaxel significantly improves survival in advanced pancreatic cancer (PC) and demonstrates better results in non-small-cell lung cancer (NSCLC) patients with squamous histology, highlighting its potential as a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. Cecco, S., Aliberti, M., Baldo, P., et al.[2015]

Nab-PTX (Abraxane®) was administered to 31 breast cancer patients without any allergic reactions, indicating it is well tolerated, even in those with alcohol intolerance.

Among patients with locally advanced operable breast cancer, higher doses (260 mg/m²) resulted in a better response rate, with 10 out of 13 showing a partial response, suggesting its efficacy in treating advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. Tauchi, Y., Kashiwagi, S., Ishihara, S., et al.[2015]

In a study of 81 women with early-stage estrogen receptor-positive breast cancer, nab-Paclitaxel showed significant antitumor activity with a good response rate (RCB 0+I) of 24.7%, indicating its effectiveness as a neoadjuvant treatment despite a higher than expected poor response rate (RCB III) of 28.4%.

The treatment was associated with low rates of severe toxicity, with neutropenia being the most common side effect, and an exploratory analysis suggested that overexpression of the SPARC protein in tumors may predict a complete response, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. Martín, M., Chacón, JI., Antón, A., et al.[2021]

In a phase 3 trial involving 902 patients with untreated metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel significantly improved progression-free survival compared to nab-paclitaxel alone, with median survival times of 7.2 months versus 5.5 months, respectively.

The combination therapy also showed promising overall survival results, particularly in patients with PD-L1-positive tumors, where median overall survival was 25.0 months for the combination versus 15.5 months for the placebo group, indicating enhanced efficacy without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. Schmid, P., Adams, S., Rugo, HS., et al.[2021]

In a study of 42 metastatic breast cancer patients who had previously been treated with taxanes, nab-paclitaxel demonstrated a 23.8% overall response rate, indicating significant antitumor activity despite prior treatment failures.

Nab-paclitaxel was well tolerated, with most treatment-related side effects being mild to moderate, suggesting a manageable safety profile for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. Fabi, A., Giannarelli, D., Malaguti, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8282704/

Clinical and biomarker results from phase I/II study of PI3K ... Alpelisib plus nab-paclitaxel combination was well-tolerated and shows encouraging efficacy, especially in patients with PIK3CA-mutated tumor/ctDNA. Impact of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04251533

NCT04251533 | Study Assessing the Efficacy and Safety of ... The purpose of this study was to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33602685/

Clinical and Biomarker Results from Phase I/II Study of PI3K ... The alpelisib plus nab-paclitaxel combination was well tolerated and shows encouraging efficacy, especially in patients with PIK3CA-mutated tumor/ctDNA.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-02353

Study Assessing the Efficacy and Safety of Alpelisib + Nab- ... The purpose of this study was to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P3-09-21/752494/Abstract-P3-09-21-Phase-IB-II-Trial-of-Alpelisib

Abstract P3-09-21: Phase IB/II Trial of Alpelisib with iNOS ... We report here the results from the Phase IB portion of this trial. Methods: Patients with metastatic or locally advanced, unresectable triple ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20493090

A Study Assessing the Effectiveness and Safety of Alpelisib ... About this study. The purpose of this study is to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in ...