Paclitaxel + Trastuzumab +/- Lapatinib for Breast Cancer

No longer recruiting at 379 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different combinations of the chemotherapy drug paclitaxel and the monoclonal antibody trastuzumab, with or without the addition of lapatinib (a targeted therapy drug), in treating operable stage II or III breast cancer. These treatments aim to shrink tumors before surgery by stopping cancer cells from growing and spreading. Participants suitable for this trial have HER2-positive breast cancer that can be surgically removed and have not received prior treatment for this cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Previous studies have found the combination of paclitaxel and lapatinib to be well-tolerated in patients with HER2-positive breast cancer. For example, one study showed that this treatment improved disease outcomes without causing severe side effects. Another study confirmed the combination's general safety, although it affected each drug's levels in the body.

When trastuzumab is added to paclitaxel and lapatinib, research indicates it remains tolerable. A study showed that using these three drugs together was safe for patients with breast cancer, meaning that while some side effects may occur, they are usually manageable and not severe.

Overall, available data suggest these treatments are relatively safe for patients, with side effects that are not extreme. However, individual reactions vary, so some people might experience side effects more than others. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the combined use of paclitaxel, trastuzumab, and lapatinib for breast cancer, aiming to enhance effectiveness against HER2-positive tumors. Unlike standard treatments that typically involve just trastuzumab and chemotherapy, adding lapatinib introduces a dual inhibition strategy, targeting both HER2 and EGFR pathways. This combination could potentially offer more robust tumor suppression and improve outcomes for patients who may not respond adequately to the conventional therapies. Additionally, lapatinib's oral administration offers a convenient alternative to intravenous therapies, potentially improving patient adherence and comfort.

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

This trial will compare different treatment combinations for HER2-positive breast cancer. Research has shown that using paclitaxel with lapatinib, which participants in Arm III (TL) may receive, can significantly improve outcomes, enhancing progression-free survival and overall treatment benefit compared to paclitaxel alone. In Arm I (THL), participants will receive paclitaxel, trastuzumab, and lapatinib. Studies have found this combination to be highly effective as a first treatment for HER2-positive metastatic breast cancer, helping patients live longer without cancer progression. Meanwhile, Arm II (TH) will involve trastuzumab and paclitaxel together, which are also effective; trastuzumab stops tumor growth, while paclitaxel prevents cancer cells from dividing and spreading. Overall, these combinations show strong promise in treating certain types of breast cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Lisa A Carey

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

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 tumor is HER2 positive, confirmed by specific tests.

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

I haven't received any treatment for this cancer.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2651098/

Phase III, Double-Blind, Randomized Study Comparing ... In 86 HER-2–positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00356811?term=LAPATINIB%20DITOSYLATE%20MONOHYDRATE&viewType=Table&rank=3&tab=results

Study Results | Lapatinib Combined With Paclitaxel For Patients ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

3. ovid.com ovid.com/journals/bcman/fulltext/10.2217/bmt.13.55~lapatinib-in-combination-with-paclitaxel-for-the-treatment

Lapatinib in combination with paclitaxel for the... : Breast Cancer ... The combination of paclitaxel and lapatinib has been shown to offer a significant survival benefit over paclitaxel alone in first-line treatment of HER2- ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT78594

A phase Ib study of preoperative lapatinib, paclitaxel, and ... Eleven of 12 patients showed clinical PR with 3 patients (25%) achieved total pCR, and 5 (42%) achieved tumor pCR. Six patients (50%) underwent breast ...

5. gsk.com gsk.com/en-gb/media/press-releases/phase-iii-study-in-her2-positive-advanced-breast-cancer-shows-overall-survival-benefit-when-tykerb-is-combined-with-paclitaxel/

Phase III study in HER2-positive advanced breast cancer ... Phase III study, women with untreated HER2+ metastatic breast cancer improved when treated with a combination of lapatinib & paclitaxel.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4666271/

Safety, pharmacokinetics and efficacy findings in an open ... The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00111787

NCT00111787 | Study Of Lapatinib In Combination With ... This Study was designed to determine how effective and safe a new investigational drug, lapatinib, is in combination with paclitaxel in treating patients ...

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.1046

Updated efficacy and safety assessment of first-line therapy ... Conclusions: Previously reported preliminary efficacy data showed a similar ORR for trastuzumab plus paclitaxel when given in combination with lapatinib. A high ...