Paclitaxel + Trastuzumab +/- Lapatinib for Breast Cancer

Recruiting at 364 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Inflammatory breast cancer, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

305 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since no prior chemotherapy, hormone therapy, biologic, or radiation therapy for this cancer is allowed, you may need to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Paclitaxel, Trastuzumab, and Lapatinib Ditosylate for breast cancer?

Research shows that combining trastuzumab with paclitaxel is effective for treating HER2-positive metastatic breast cancer, improving survival rates. Trastuzumab, when used with chemotherapy, is a standard treatment for HER2-positive breast cancer, and adding paclitaxel has shown increased antitumor activity. ^{1 2 3 4 5}

What safety data exists for the combination of Paclitaxel and Trastuzumab in breast cancer treatment?

Paclitaxel and Trastuzumab have been used together in treating HER2-positive breast cancer, but Paclitaxel can cause hair loss, nerve damage, and allergic reactions. Trastuzumab is generally safe but can have heart-related side effects, especially when used with other drugs. ^{1 6 7 8 9}

What makes the drug combination of Paclitaxel, Trastuzumab, and Lapatinib unique for breast cancer treatment?

This drug combination is unique because it targets HER2-positive breast cancer, with Trastuzumab and Lapatinib both focusing on the HER2 receptor, which is overexpressed in some breast cancers, while Paclitaxel is a chemotherapy drug that helps stop cancer cell growth. This combination may offer a more comprehensive approach by attacking the cancer cells in multiple ways. ^{4 5 10 11 12}

What is the purpose of this trial?

This randomized phase III trial studies paclitaxel and trastuzumab with or without lapatinib to see how well they work in treating patients with stage II or stage III breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as 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. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.

Research Team

Lisa A Carey

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for patients with stage II or III breast cancer that can be surgically removed. Participants must not have metastatic disease, should have normal liver function and heart health, know their hormone receptor status, agree to provide biopsies, and not be pregnant or breastfeeding. Prior treatments for this cancer are disallowed. Tumors must be HER2 positive.

Inclusion Criteria

My cancer is at stage III and has been checked for spread.

My tumor is HER2 positive, confirmed by specific tests.

I haven't received any treatment for this cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant therapy with paclitaxel, trastuzumab, and/or lapatinib for 16 weeks

16 weeks

Weekly visits for IV administration

Surgery

Participants undergo definitive surgery (breast conservation or total mastectomy) within 42 days after completion of neoadjuvant therapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 6 months for 2 years, then annually

Treatment Details

Interventions

• Lapatinib Ditosylate
• Paclitaxel
• Trastuzumab

Trial Overview The study tests the effectiveness of paclitaxel and trastuzumab with or without lapatinib before surgery in shrinking tumors. Paclitaxel is a chemotherapy drug; trastuzumab is a monoclonal antibody blocking tumor growth; lapatinib inhibits enzymes needed by tumor cells.

Participant Groups

Group I: Arm III (TL) Experimental Treatment 2 Interventions

Patients receive paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)

Group II: Arm I (THL) Experimental Treatment 4 Interventions

Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.

Group III: Arm II (TH) Active Control 3 Interventions

Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m\^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 40 patients with HER2-positive metastatic breast cancer, the combination of trastuzumab, paclitaxel, and capecitabine resulted in a high overall response rate of 81.1%, with 24.3% achieving complete responses and 56.8% partial responses.

The treatment was well-tolerated, with manageable grade 3 adverse events, indicating that this combination therapy is both effective and safe for first-line treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. Tonyali, O., Benekli, M., Berk, V., et al.[2021]

In a study of 30 patients with early-stage HER2+ breast cancer, the combination of trastuzumab and vinorelbine (TV) showed a high 5-year invasive disease-free survival rate of 90.9% and a perfect overall survival rate of 100% after a median follow-up of 68 months.

TV was well tolerated, with no cases of alopecia or long-term neuropathy reported, making it a promising alternative for patients who wish to avoid the side effects associated with traditional taxane-based regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer. McLaughlin, S., Nakajima, E., Bar, Y., et al.[2023]

In a study of 17 patients with advanced HER2/neu overexpressing breast cancer, the combination of trastuzumab and paclitaxel resulted in a response rate of 59%, with 2 complete responses and a median overall survival of 23 months.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced significant toxicities, including hypersensitivity reactions and grade 3 neuropathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4-years results of weekly trastuzumab and paclitaxel in the treatment of women with HER2/neu overexpressing advanced breast cancer: single institution prospective study. Janku, F., Pribylova, O., Zimovjanova, M., et al.[2015]

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

Standard treatments for breast cancer after initial chemotherapy include capecitabine, S-1, vinorelbine, irinotecan, or gemcitabine, which are effective options for managing the disease.

Newer therapies like lapatinib for trastuzumab-resistant cases and combinations like bevacizumab with taxanes show promise, highlighting the need for further research on optimal drug sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab]. Ito, Y., Kobayashi, K.[2016]

In a study of 152 patients with HER2-positive metastatic breast cancer, the combination of taxanes with trastuzumab and pertuzumab showed a significant progression-free survival (PFS) advantage over vinorelbine in patients with newly diagnosed metastatic disease, indicating a potential benefit for this specific group.

Overall, there was no significant difference in overall survival (OS) between the two treatment groups, suggesting that both taxanes and vinorelbine are viable options when combined with trastuzumab and pertuzumab for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. Reinhorn, D., Kuchuk, I., Shochat, T., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Trastuzumab retreatment after relapse on adjuvant trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer: final results of the Retreatment after HErceptin Adjuvant trial. [2022]

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

Pilot trial of trastuzumab starting with or after the doxorubicin component of a doxorubicin plus paclitaxel regimen for women with HER2-positive advanced breast cancer. [2022]

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

Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. [2023]

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

Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of Trastuzumab and Paclitaxel plus Capecitabine in the first-line treatment of HER2-positive metastatic breast cancer. [2021]

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

Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

In vitro comparative evaluation of trastuzumab (Herceptin) combined with paclitaxel (Taxol) or docetaxel (Taxotere) in HER2-expressing human breast cancer cell lines. [2020]

8. France pubmed.ncbi.nlm.nih.gov

4-years results of weekly trastuzumab and paclitaxel in the treatment of women with HER2/neu overexpressing advanced breast cancer: single institution prospective study. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab]. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Cutaneous photosensitivity induced by paclitaxel and trastuzumab therapy associated with aberrations in the biosynthesis of porphyrins. [2015]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. [2021]