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

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well nab-paclitaxel and alpelisib works in treating patients with triple negative breast cancer with PIK3CA or PTEN alterations that does not respond to anthracycline chemotherapy (anthrocycline refractory). Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nab-paclitaxel and alpelisib before surgery may help shrink the tumor before surgery.

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.

What data supports the effectiveness of the drug Nab-paclitaxel + Alpelisib for Triple Negative Breast Cancer?

Research shows that nanoparticle albumin-bound paclitaxel (nab-paclitaxel) can enhance the activity and reduce the toxicity of cancer treatments, and it has shown effectiveness in breast and pancreatic cancers. This suggests that nab-paclitaxel may be a promising component in treating aggressive forms of breast cancer, like triple-negative breast cancer. ^{1 2 3 4 5}

Is the combination of Nab-paclitaxel and Alpelisib safe for humans?

Nab-paclitaxel, a key component of the treatment, is generally considered safe and is used in treating various cancers, including breast cancer, without needing premedication to prevent allergic reactions. It has been shown to cause mild to moderate nerve-related side effects in some patients, but severe reactions are rare. ^{3 4 6 7 8}

What makes the drug Nab-paclitaxel + Alpelisib unique for treating triple-negative breast cancer?

Nab-paclitaxel is a unique form of paclitaxel that uses albumin nanoparticles to deliver the drug more effectively, potentially enhancing its activity and reducing toxicity. This combination with Alpelisib, which targets specific cancer cell pathways, offers a novel approach for treating triple-negative breast cancer, a condition with limited treatment options. ^{1 3 5 9 10}

Research Team

Senthilkumar Damodaran

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. [2021]

2. New Zealand 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. [2022]

3. Egypt pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time? [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04). [2023]

6. United States 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). [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

[Clinical experience of nab-Paclitaxel treatment in 31 patients with breast cancer]. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy evaluation of albumin-bound paclitaxel. [2015]

9. England 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. [2021]

10. India pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy in HER2-negative breast cancer. [2022]