Neoadjuvant Therapy for Breast Cancer

(BRE-10 Trial)

Overseen By Mercedes Carrasquillo, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Must not be taking: Antivirals altering metabolism

Disqualifiers: Prior therapy, Active infection, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for early-stage HER2-positive breast cancer. Researchers are testing the effectiveness of several chemotherapy drugs, including docetaxel (also known as Taxotere, Docefrez, Docivyx, DTX, or DXL), nab-paclitaxel, and paclitaxel, which are often used to shrink tumors before surgery. The trial seeks adults diagnosed with HER2-positive breast cancer who plan to undergo surgery to remove the tumor. Participants should not have received any prior treatment for this cancer and must meet certain health criteria to ensure safety. As a Phase 2 trial, the research focuses on measuring how well the treatment works in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications that alter the metabolism or tolerability of the trial drugs, you may need to adjust them. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments like docetaxel, nab-paclitaxel, paclitaxel, trastuzumab, and pertuzumab are generally well-tolerated for breast cancer, though each has specific safety considerations.

Docetaxel has been used safely in early breast cancer patients in the Asia-Pacific region, but it may cause side effects such as low white blood cell counts and fluid retention.

Nab-paclitaxel is known for manageable side effects, though it can lead to low blood cell counts. It is often better tolerated than some other similar cancer drugs.

Paclitaxel is another common treatment that is generally safe, but it can sometimes cause serious side effects like low blood cell counts or infections.

Trastuzumab targets HER2-positive breast cancer and is generally safe, though some patients might experience heart-related side effects. It is well-researched and often used with other drugs.

Pertuzumab also treats HER2-positive breast cancer. It is mostly safe but can cause diarrhea and hair loss. In some cases, more severe allergic reactions have been reported.

Overall, these treatments have established safety records, but individual responses can vary. Patients should discuss potential risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this neoadjuvant therapy for breast cancer because it offers a customizable approach using a combination of taxanes and targeted therapies like trastuzumab and pertuzumab. Unlike standard chemotherapy options, which often have a one-size-fits-all approach, this treatment allows physicians to choose between paclitaxel, nab-paclitaxel, or docetaxel based on patient tolerance and specific needs. Additionally, the incorporation of targeted therapies like trastuzumab and pertuzumab helps directly attack cancer cells with human epidermal growth factor receptor 2 (HER2) overexpression, potentially improving outcomes. This personalized and precise approach could lead to more effective and less toxic treatment regimens for breast cancer patients.

What evidence suggests that this trial's treatments could be effective for HER2-positive breast cancer?

Research has shown that the drugs docetaxel, nab-paclitaxel, and paclitaxel effectively treat breast cancer. In this trial, participants will receive one of these taxane options based on the physician's choice. Docetaxel has a high success rate, with 94% of patients responding to treatment, and some even experience a complete disappearance of cancer. Nab-paclitaxel works well for aggressive tumors, increasing the chances of removing cancer cells before surgery. Paclitaxel is similarly effective, with over 25% of patients seeing their cancer completely disappear. For patients with HER2-positive breast cancer, this trial also includes the option to combine trastuzumab and pertuzumab with chemotherapy. Studies have found that this combination can shrink tumors more effectively and improve survival rates. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early-stage HER2-positive breast cancer, as confirmed by specific tests. They should be fit enough for chemotherapy and surgery to remove the breast tumor and examine nearby lymph nodes. There must be no signs of cancer spread elsewhere in the body.

Inclusion Criteria

My breast cancer was confirmed by a biopsy within the last 90 days.

My cancer is HER2-positive based on specific tests.

My cancer has not spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy with Taxane options and HER2-targeted therapy

16 weeks

Weekly visits for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular visits for safety and quality of life assessments

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Nab-paclitaxel
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview

The study is testing how well different chemotherapy drugs (Docetaxel, Trastuzumab, Pertuzumab, Paclitaxel, Nab-paclitaxel) work before surgery in patients whose tumors have a certain genetic profile indicating they are likely to respond to treatment.

How Is the Trial Designed?

Group I: Single Treatment Arm Experimental Treatment 5 Interventions

One of the following Taxane options below per physician's choice * Paclitaxel 80mg/m2 IV D1, 8, 15 Q21 days * Nab-paclitaxel1 125mg/m2 IV D1, 8, 15 Q21 days * Docetaxel1 75mg/m2 IV D1 Q-21 days * Trastuzumab2 8mg/kg loading, then 6mg/kg IV/SQ D1 Q21 days * Pertuzumab2 840 mg loading, then 420mg IV/SQ D1 Q21 days * 1 may be substituted for paclitaxel for patients intolerant to paclitaxel or the steroid premed regimen, or at investigator discretion * 2 Pertuzumab, trastuzumab, and hyaluronidase injection for subcutaneous use may be substituted with dose per package insert

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

In a retrospective study of breast cancer patients receiving neoadjuvant systemic treatment from 2013 to 2022, nanoparticle albumin-bound paclitaxel (Nab-P) was found to significantly improve total pathological complete response (total-pCR) and breast pathological complete response (breast-pCR) rates compared to other taxanes.

The choice of taxane was identified as an independent risk factor for achieving total-pCR and breast-pCR, suggesting that Nab-P should be prioritized as the first-line treatment option among taxanes for neoadjuvant therapy in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer. Zhang, W., Wang, Y., He, J., et al.[2023]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

In a study of 159 HER2-negative breast cancer patients, nab-paclitaxel showed a significantly higher pathological complete response (pCR) rate compared to docetaxel (36.71% vs 20.00%), indicating it may be more effective as neoadjuvant chemotherapy.

Despite the higher pCR rate with nab-paclitaxel, there was no significant difference in disease-free survival (DFS) between the two groups (82.28% for nab-paclitaxel vs 76.25% for docetaxel), and nab-paclitaxel was associated with a higher incidence of peripheral sensory neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Albumin-Bound Paclitaxel Compared to Docetaxel as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer. Lv, ZD., Song, HM., Niu, ZH., et al.[2022]

The nanosomal docetaxel lipid suspension (NDLS) formulation showed a better overall therapeutic response rate of 35.5% compared to 26.3% for the traditional Taxotere in metastatic breast cancer patients, based on a study involving 72 patients.

NDLS can be administered without the need for premedication with corticosteroids, and its safety profile is comparable to that of Taxotere, making it a promising alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of a novel nanosomal docetaxel lipid suspension compared with taxotere in locally advanced or metastatic breast cancer patients. Ahmad, A., Sheikh, S., Taran, R., et al.[2018]

In a study of 19 metastatic breast cancer patients who were resistant to docetaxel treatment, 26.3% had BRCA1 mutations, with a significant association found in those with triple-negative breast cancer (71% of BRCA1 mutation carriers).

The findings suggest that BRCA1 testing should be considered for triple-negative breast cancer patients who do not respond to docetaxel, as it may help identify hereditary mutations in families without a known history of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary resistance to docetaxel-based chemotherapy in metastatic breast cancer patients correlates with a high frequency of BRCA1 mutations. Wysocki, PJ., Korski, K., Lamperska, K., et al.[2018]

In a study involving women with metastatic breast cancer (MBC) who had previously failed taxane therapy, albumin-bound paclitaxel showed response rates of 14% and 16% for doses of 100 mg/m2 and 125 mg/m2, respectively, indicating its potential effectiveness in this patient population.

The 100 mg/m2 dose of albumin-bound paclitaxel not only demonstrated similar antitumor activity to the higher dose but also had a more favorable safety profile, with low rates of severe side effects like hypersensitivity reactions and grade 4 neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. Blum, JL., Savin, MA., Edelman, G., et al.[2023]

In a study of 91 breast cancer patients treated with nanosomal docetaxel lipid suspension (NDLS), the treatment showed a 100% overall response rate (ORR) in the neoadjuvant setting and a 64.7% ORR in the metastatic setting, indicating strong efficacy.

NDLS-based chemotherapy was well tolerated, with 59.3% of patients experiencing at least one adverse event, primarily hematological issues like anemia and neutropenia, but no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Breast Cancer: Results from a Multicenter Retrospective Study. Subramanian, S., Prasanna, R., Biswas, G., et al.[2023]

Docetaxel, an anticancer drug, is associated with hypersensitivity reactions and fluid retention due to its formulation with polysorbate 80, prompting research for safer alternatives.

New formulations of docetaxel, such as PEGylated liposomes and nanoparticle-aptamer bioconjugates, aim to enhance targeting of cancer cells while reducing side effects, showing promise in improving the drug's efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative drug formulations of docetaxel: a review. Engels, FK., Mathot, RA., Verweij, J.[2022]

In a study involving 152 patients with HER2- early-stage breast cancer, weekly nab-paclitaxel showed comparable efficacy to docetaxel in achieving pathologic complete response (pCR) rates, with 12% for docetaxel and 17% for nab-paclitaxel, indicating it is a viable alternative for neoadjuvant chemotherapy.

Nab-paclitaxel was associated with a similar incidence of severe adverse events compared to docetaxel, but notably, it did not cause any grade 3/4 peripheral sensory neuropathy, suggesting a better safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Multicenter Phase II Trial of Neoadjuvant Therapy Comparing Weekly Nab-paclitaxel Followed by FEC With Docetaxel Followed by FEC in HER2- Early-stage Breast Cancer. Kuwayama, T., Nakamura, S., Hayashi, N., et al.[2022]

Albumin-bound paclitaxel has demonstrated significant clinical efficacy in treating metastatic breast cancer, as shown in phase II and III trials, making it a promising alternative to standard formulations.

This formulation is associated with better tolerance and safety compared to traditional solvent-based paclitaxel, suggesting it may reduce adverse effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel: the benefit of this new formulation in the treatment of various cancers. Montana, M., Ducros, C., Verhaeghe, P., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2741049/

Neoadjuvant docetaxel for operable breast cancer induces a ...

For patients with initially responsive tumours, the sequential use of docetaxel also gave better results (94% clinical response and 34% pCR rates) than further ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.11600

Efficacy of neoadjuvant weekly docetaxel in locally ...

Results: The clinical response rate was 50%, including 29% complete responses. 4 patients (29%) had stable disease and 3 patients (21%) progressed while on ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/9364536/

Docetaxel as neoadjuvant chemotherapy in patients with ...

A partial response was achieved in 22 patients (67%), with 6 patients (18%) experiencing a complete response with this regimen. One patient with a complete ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1526820924000521

Long-Term Outcomes of S-1 Combined With Low-Dose ...

Furthermore, 81.9% of patients could take S-1 at >80% of the required dose, and the adverse events were acceptable. Finally, we concluded that our regimen was ...

5.

aacrjournals.org

aacrjournals.org/clincancerres/article/9/2/686/203745/Weekly-Docetaxel-as-Neoadjuvant-Chemotherapy-for

Weekly Docetaxel as Neoadjuvant Chemotherapy for Stage II ...

Preliminary results show that the addition of docetaxel as neoadjuvant treatment provides a benefit in terms of pCR and overall response rate (25 and 91%, ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2013/020449s071lbl.pdf

Taxotere (docetaxel) Label - accessdata.fda.gov

WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA,. HYPERSENSITIVITY REACTIONS, and FLUID RETENTION. See full prescribing information for complete boxed ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4705087/

Based Chemotherapy in Early Breast Cancer Patients ...

Docetaxel-based chemotherapy did not show any significant safety concerns for early breast cancer patients of the Asia-Pacific region.

8.

products.sanofi.us

products.sanofi.us/taxotere/taxotere.html

TAXOTERE® (docetaxel) injection, for intravenous use

Table 11 summarizes the safety data obtained from patients that received induction chemotherapy with TAXOTERE 75 mg/m2 in combination with cisplatin and ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2012/201525s002lbl.pdf

Docetaxel label - accessdata.fda.gov

The safety profile is generally similar in patients receiving docetaxel for the treatment of breast cancer and in patients with other tumor types (See Table 3).

10.

ema.europa.eu

ema.europa.eu/en/documents/product-information/taxotere-epar-product-information_en.pdf

Taxotere, INN-Docetaxel - European Medicines Agency

TAXOTERE monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous ...