Chemotherapy + Trastuzumab for Early-Stage HER2 Positive Breast Cancer

No longer recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Nebraska

Disqualifiers: Prior malignancy, Peripheral neuropathy, 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: 26

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining chemotherapy drugs (cyclophosphamide and paclitaxel) with a targeted therapy drug (trastuzumab) to treat early-stage HER2 positive breast cancer. This cancer type has spread to nearby lymph nodes but not beyond. The trial aims to determine if this treatment can prevent cancer from returning after surgery. Women diagnosed with stage I-II HER2 positive breast cancer who have completed surgery may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer.

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

Research has shown that the combination of cyclophosphamide, paclitaxel, and trastuzumab is generally well-tolerated by patients with HER2-positive breast cancer. These drugs work together to stop cancer cells from growing.

In earlier studies, patients received a similar treatment before surgery. Most managed the treatment well, though some experienced side effects. Common side effects included tiredness, nausea, and hair loss, which are typical with chemotherapy.

Trastuzumab, often used in breast cancer treatments, targets HER2-positive cancer cells effectively. While usually safe, it can sometimes affect the heart, so doctors monitor patients closely during treatment.

Overall, this treatment shows promise for early-stage HER2-positive breast cancer, with side effects that most patients can manage. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of chemotherapy and trastuzumab for early-stage HER2 positive breast cancer because it offers a targeted approach not seen in all standard treatments. Trastuzumab specifically targets the HER2 protein, which can promote the growth of cancer cells, providing a more precise attack on cancer compared to traditional chemotherapy alone. This combination aims to enhance treatment effectiveness while potentially reducing the overall side effects experienced by patients. Additionally, the maintenance therapy with trastuzumab offers a prolonged treatment phase that may help in keeping the cancer at bay, which is a promising aspect for long-term management.

What evidence suggests that this treatment might be an effective treatment for HER2 positive breast cancer?

Research has shown that a combination of three drugs—cyclophosphamide, paclitaxel, and trastuzumab (PC-H)—is effective for treating early-stage HER2-positive breast cancer. In this trial, participants will receive this combination treatment. Studies have found that adding trastuzumab to chemotherapy reduces the chances of cancer recurrence and decreases the risk of death by about one-third. This treatment is generally safe and has a high success rate in keeping patients cancer-free. Specifically, some studies reported that 84% of patients remained disease-free five years after receiving trastuzumab with their chemotherapy. These results suggest that this combination can be a strong option to help prevent cancer from returning after surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Amulya Yellala, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for women with stage I-II HER2/neu positive breast cancer post-surgery. Participants must have normal organ function, not be pregnant or nursing, agree to use birth control, and have no history of severe illnesses or conditions that could interfere with the study.

Inclusion Criteria

Your alkaline phosphatase level should not be more than 1.5 times the upper limit of normal within 30 days before joining the trial.

Your total bilirubin level has to be within a certain range in the last 30 days before joining the study.

Your liver function tests should not be more than 1.5 times the upper limit of normal within the last 30 days before joining the trial.

Exclusion Criteria

I have had cancer before, but it was either skin cancer treated successfully or a non-spreading type.

Pregnant or nursing women

Known hypersensitivity to any component of required drugs in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Systemic Therapy

Patients receive cyclophosphamide, paclitaxel, and trastuzumab intravenously on day 1, repeated every 14 days for 6 courses

12 weeks

6 visits (in-person)

Maintenance Trastuzumab Therapy

Patients receive trastuzumab intravenously every 21 days for up to 52 weeks

52 weeks

Approximately 17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Paclitaxel
• Trastuzumab

Trial Overview

The effectiveness and side effects of cyclophosphamide, paclitaxel, and trastuzumab are being tested after surgery in patients with early-stage HER2-positive breast cancer. The goal is to prevent cancer recurrence by using these chemotherapy drugs and a monoclonal antibody.

How Is the Trial Designed?

Group I: Treatment (cyclophosphamide, paclitaxel, trastuzumab) Experimental Treatment 4 Interventions

SYSTEMIC THERAPY: Patients receive cyclophosphamide IV over 1 hour, paclitaxel IV over 3 hours, and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE TRASTUZUMAB THERAPY: Beginning in course 6, patients receive trastuzumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo radiation therapy at the discretion of the radiation oncologist and medical oncologist and patients with estrogen/progesterone receptor positive tumors receive hormonal therapy as determined by the medical oncologist per standard NCCN guidelines.

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 involving 397 patients with HER2-positive early breast cancer, treatment with pertuzumab and trastuzumab alongside anthracycline-containing regimens showed a low incidence of serious cardiac events, with only 1.5% experiencing class III/IV heart failure and 6.5% having declines in left ventricular ejection fraction in one treatment cohort.

The pathologic complete response (pCR) rates were high, at 61.8% and 60.7% for the two treatment cohorts, indicating that this combination therapy is both effective and maintains a favorable safety profile, consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Swain, SM., Ewer, MS., Viale, G., et al.[2022]

Trastuzumab significantly improves treatment outcomes for women with HER2 positive breast cancer, as shown in four large randomized trials.

The main safety concerns associated with trastuzumab are serious infusion-related reactions and cardiotoxicity, highlighting the need to weigh the benefits against these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. Svetlovska, D., Mardiak, J., Kristova, V.[2016]

In a study of 210 patients with ERBB2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab without chemotherapy showed a 24-month overall survival rate of 79.0%, which is comparable to 78.1% for those receiving the combination with chemotherapy.

Patients receiving the chemotherapy-free regimen had a median progression-free survival of 8.4 months, significantly shorter than the 23.3 months for those who received chemotherapy, but the absence of chemotherapy resulted in fewer adverse events and slight improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Huober, J., Weder, P., Ribi, K., et al.[2023]

Trastuzumab (Herceptin) has demonstrated significant antitumor activity in patients with HER-2-positive metastatic breast cancer, improving response and survival rates when combined with first-line chemotherapy.

Recent clinical trials have focused on new chemotherapy approaches for node-positive breast cancer, laying the groundwork for ongoing studies that incorporate trastuzumab into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. Perez, EA., Hortobagyi, GN.[2015]

In a study of 55 patients with early-stage, HER2-positive breast cancer, the neoadjuvant chemotherapy regimen combining epirubicin, cyclophosphamide, docetaxel, trastuzumab, and pertuzumab resulted in a high complete pathologic response rate of 64.8%.

The regimen demonstrated good cardiac safety, with only one case of significant left ventricular ejection fraction (LVEF) decline and no instances of symptomatic heart dysfunction, indicating that the treatment can be administered without major cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients. Douganiotis, G., Grigoriadis, S., Kontovinis, L., 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]

Trastuzumab (Herceptin) combined with endocrine therapy is a promising treatment for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer, while for aggressive HER2-positive cases, it significantly improves survival when used with chemotherapy, particularly taxanes.

Trastuzumab has a favorable safety profile, adding little toxicity to taxane chemotherapy, and enhances quality of life compared to chemotherapy alone, making it a viable option for patients who may not tolerate cytotoxic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximizing clinical benefit with trastuzumab. Bell, R., Verma, S., Untch, M., et al.[2019]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1526820924001848

Clinical Breast Cancer

PC-H demonstrated overall safety and efficacy, yielding high rates of relapse-free survival among patients with early stage (HER2+) breast cancer.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39261255/

Investigating the Efficacy and Safety of a Dose-Dense ...

Conclusions: PC-H demonstrated overall safety and efficacy, yielding high rates of relapse-free survival among patients with early stage (HER2+) breast cancer.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8324484/

Trastuzumab for early-stage, HER2-positive breast cancer

Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces recurrence of and mortality from breast cancer by a third, ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa0910383

Adjuvant Trastuzumab in HER2-Positive Breast Cancer

The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, ...

5.

nature.com

nature.com/articles/s41598-022-05209-8

Efficacy of adjuvant trastuzumab in women with HER2- ...

Adjuvant trastuzumab has been associated with superior survival in women with ≥ T1c or node-positive HER2-positive early-stage breast cancer.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40399223/

Safety and Effectiveness of Adriamycin ...

ACTH-O regimen is a viable alternative to standard anthracycline-based regimens in HER2+ early breast cancer. It offers similar long-term outcomes while ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01750073

NCT01750073 | Paclitaxel & Cyclophosphamide With or ...

This phase II trial studies the side effects and how well giving paclitaxel and cyclophosphamide with or without trastuzumab before surgery works in ...

8.

hemonc.org

hemonc.org/wiki/Early_breast_cancer,_HER2-positive

Early breast cancer, HER2-positive

ddAC-THP (Paclitaxel). ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab

9.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2001.19.10.2587

Weekly Trastuzumab and Paclitaxel Therapy for Metastatic ...

This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer.

10.

lbbc.org

lbbc.org/about-breast-cancer/treatments/chemotherapy/common-regimens/th-paclitaxel

TH Chemotherapy Regimen

TH (paclitaxel and trastuzumab) is a chemotherapy regimen used to treat HER2-positive breast cancer. It is a combination of two medicines.