Chemotherapy + Trastuzumab for Early-Stage HER2 Positive Breast Cancer

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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of chemotherapy and trastuzumab for early-stage HER2-positive breast cancer?

Research shows that trastuzumab, when combined with chemotherapy, improves survival and clinical outcomes in patients with HER2-positive breast cancer. This combination is considered the standard of care for both early and metastatic stages of the disease. ^{1 2 3 4 5}

Is the combination of chemotherapy and trastuzumab safe for early-stage HER2-positive breast cancer?

The combination of chemotherapy and trastuzumab for early-stage HER2-positive breast cancer has been studied for safety, particularly regarding heart health. Some studies report a risk of heart-related side effects, but these treatments are generally well-tolerated with careful monitoring. ^{6 7 8 9 10}

How is the drug combination of chemotherapy and trastuzumab unique for early-stage HER2-positive breast cancer?

The combination of chemotherapy and trastuzumab is unique because it targets HER2-positive breast cancer by using trastuzumab, a drug that specifically binds to the HER2 protein on cancer cells, along with chemotherapy to enhance the treatment's effectiveness. This approach is different from using chemotherapy alone, as trastuzumab helps improve survival rates and quality of life by specifically targeting cancer cells with minimal additional toxicity. ^{1 2 3 4 6}

What is the purpose of this trial?

This phase II trial studies the side effects and how well cyclophosphamide, paclitaxel, and trastuzumab work when given after surgery in treating patients with stage I-II human epidermal growth factor receptor (HER2/neu) positive breast cancer (confined to the breast or the breast and lymph nodes under the arm). Drugs used in chemotherapy, such as cyclophosphamide and 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, may interfere with the ability of tumor cells to grow and spread. Giving cyclophosphamide, paclitaxel, and trastuzumab after surgery may help prevent the cancer from coming back.

Research Team

Amulya Yellala, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

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

I am able to follow the treatment plan as directed.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

References

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

Maximizing clinical benefit with trastuzumab. [2019]

2. 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]

3. United States 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. [2023]

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

Ongoing and planned adjuvant trials with trastuzumab. [2015]

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

Adjuvant trastuzumab in HER2-positive breast cancer. [2022]

6. Cyprus 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. [2021]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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

9. England 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. [2022]

10. Slovakia pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. [2016]