Chemotherapy +/− Trastuzumab for Breast Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Nebraska

Must not be taking: Antiemetics, Investigational agents

Disqualifiers: Inflammatory breast cancer, Metastatic disease, Prior chemotherapy, 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: 9

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies the side effects and how well giving paclitaxel and cyclophosphamide with or without trastuzumab before surgery works in treating patients with previously untreated breast cancer. Drugs used in chemotherapy, such as paclitaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, may block tumor growth in different ways by targeting certain cells. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on any investigational agents or have had chemotherapy or endocrine therapy for cancer, you may not be eligible to participate.

Is the combination of chemotherapy and trastuzumab generally safe for treating breast cancer?

Trastuzumab, when combined with chemotherapy, is generally considered safe for treating HER2-positive breast cancer, but it can have side effects like heart issues and requires careful monitoring. Common side effects of trastuzumab deruxtecan include blood and stomach problems, and it has a warning for lung issues, so patients need to be monitored closely. ^{1 2 3 4 5}

How is the drug combination of Cyclophosphamide, Paclitaxel, and Trastuzumab unique for treating breast cancer?

This drug combination is unique because it includes Trastuzumab, which specifically targets HER2-positive breast cancer cells, improving survival rates when added to chemotherapy. Unlike some other regimens, it avoids anthracyclines, reducing the risk of heart-related side effects. ^{2 6 7 8 9}

What data supports the effectiveness of the drug Trastuzumab when combined with chemotherapy for breast cancer?

Research shows that adding Trastuzumab to chemotherapy significantly improves survival and disease-free outcomes for women with HER2-positive breast cancer, compared to chemotherapy alone. ^{2 7 10 11 12}

Who Is on the Research Team?

Amulya C Yellala, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for women with invasive breast cancer without distant metastases, a tumor size of at least 1 cm, and no severe illnesses that would prevent consent. Participants must have normal organ function, not be pregnant or nursing, agree to use birth control, and can't have had certain prior treatments or other cancers.

Inclusion Criteria

Non-pregnant and non-nursing women of reproductive potential agreeing to employ effective birth control

You have at least one spot that can be measured using a mammogram, ultrasound, or MRI.

Your alkaline phosphatase level is not more than 1.5 times the normal limit.

Exclusion Criteria

Known anaphylactic reaction or allergy to chemotherapy agents or appropriate antiemetics

I do not have any unmanaged ongoing illnesses.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Patients receive paclitaxel and cyclophosphamide, with HER2-positive patients also receiving trastuzumab. Treatment repeats every 14 days for up to 6 courses.

12 weeks

6 visits (in-person)

Surgery

Patients undergo mastectomy or breast conserving surgery 4-8 weeks after neoadjuvant therapy.

4-8 weeks

Post-Surgery/Systemic Therapy

HER2-positive patients receive trastuzumab and radiation therapy. ER/PR positive patients receive hormonal therapy. Triple negative patients receive doxorubicin and radiation therapy.

Up to 39 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2 years

Every 3 months for 2 years, then annually for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Laboratory Biomarker Analysis
• Paclitaxel
• Radiation Therapy
• Therapeutic Conventional Surgery
• Trastuzumab

Trial Overview The study tests how well paclitaxel and cyclophosphamide chemotherapy work with or without trastuzumab (a monoclonal antibody) before surgery in patients with untreated breast cancer. The goal is to shrink the tumor and limit surgery to remove less tissue.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, surgery, post-operative therapy) Experimental Treatment 7 Interventions

See Detailed Description

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

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 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 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]

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

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) 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]

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. 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]

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

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

3. Germany pubmed.ncbi.nlm.nih.gov

Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab in patients with primary breast cancer: a pilot study. [2018]

4. 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]

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

Pathologic complete response to preoperative sequential doxorubicin/cyclophosphamide and single-agent taxane with or without trastuzumab in stage II/III HER2-positive breast cancer. [2021]

6. 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]

7. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023]

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

[Role of the combination of trastuzumab and taxanes in the therapeutic management of cancer of the breast: from preclinical data to clinical application]. [2018]

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

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

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

Ongoing and planned adjuvant trials with trastuzumab. [2015]

11. Netherlands pubmed.ncbi.nlm.nih.gov

HER2-positive metastatic breast cancer: a changing scenario. [2019]

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

Maximizing clinical benefit with trastuzumab. [2019]