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

Trial Summary

What is the purpose of this trial?

Adult men and women with early-stage, IHC/FISH-defined HER2-positive breast cancer will have a MammaPrint®/BluePrint® assay performed on the diagnostic biopsy specimen, ordered by the treating Oncologist as standard care

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.

What data supports the effectiveness of this drug for breast cancer?

Research shows that nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is more effective and has fewer side effects than docetaxel in treating metastatic breast cancer. It also has a higher response rate and longer survival time compared to conventional paclitaxel. ^{1 2 3 4 5}

Is neoadjuvant therapy for breast cancer using docetaxel and paclitaxel generally safe?

Docetaxel and paclitaxel, used in breast cancer treatment, have been associated with side effects like hypersensitivity reactions and fluid retention. However, newer formulations like albumin-bound paclitaxel and nanosomal docetaxel lipid suspension have shown better tolerance and reduced toxicity in clinical studies. ^{1 3 6 7 8}

How is the neoadjuvant therapy for breast cancer using Docetaxel, Nab-paclitaxel, Paclitaxel, Pertuzumab, and Trastuzumab different from other treatments?

This treatment is unique because it combines multiple drugs, including nanoparticle albumin-bound paclitaxel, which has shown greater efficacy and less toxicity compared to traditional docetaxel in some studies. The use of these specific drugs together may offer a novel approach to treating breast cancer, especially in cases where other treatments have been less effective. ^{1 4 5 9 10}

Eligibility Criteria

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

I am 18 years old or older.

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

My cancer is HER2-positive based on specific tests.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

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 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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel: the benefit of this new formulation in the treatment of various cancers. [2018]

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

Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Albumin-Bound Paclitaxel Compared to Docetaxel as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Alternative drug formulations of docetaxel: a review. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Breast Cancer: Results from a Multicenter Retrospective Study. [2023]

8. United States 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. [2018]

9. United States 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. [2023]

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

Primary resistance to docetaxel-based chemotherapy in metastatic breast cancer patients correlates with a high frequency of BRCA1 mutations. [2018]