Chemotherapy +/− Trastuzumab for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of chemotherapy drugs, with or without a targeted therapy called trastuzumab, can shrink breast tumors before surgery. The trial focuses on paclitaxel and cyclophosphamide, which stop cancer cells from growing, and trastuzumab, which targets specific cells to block tumor growth. Women with newly diagnosed invasive breast cancer, without spread to distant parts of the body, may be suitable for this study. The goal is to determine if these treatments can reduce tumor size and potentially minimize the tissue removed during surgery. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

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

Research has shown that trastuzumab, when combined with chemotherapy, is generally well-tolerated by patients with HER2-positive breast cancer. Studies have demonstrated that adding trastuzumab can significantly improve survival rates. For instance, one study found that including trastuzumab with chemotherapy increased 10-year survival from 75% to 84%.

While trastuzumab is usually safe, it can cause some side effects. Common issues include heart problems and allergic reactions, but these are closely monitored during treatment.

The chemotherapy drugs in this trial, paclitaxel and cyclophosphamide, have been well-researched. They work by stopping cancer cells from growing. Common side effects include hair loss, nausea, and tiredness. Most patients handle these drugs well, but side effects can vary from person to person.

Overall, the treatments in this trial have been used before and are known to be effective. However, like all treatments, they come with some risks. In a clinical trial, researchers carefully monitor patients for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Trastuzumab with chemotherapy for breast cancer because it targets the HER2 protein, which is overexpressed in some breast cancers. Unlike standard chemotherapy that attacks all rapidly dividing cells, Trastuzumab specifically targets cancer cells with high levels of HER2, potentially leading to more effective treatment with fewer side effects. This targeted approach not only enhances the effectiveness of traditional chemotherapy agents like Cyclophosphamide and Paclitaxel but also offers hope for better outcomes in patients with HER2-positive breast cancer.

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

Research has shown that trastuzumab, one of the treatments in this trial, greatly lowers the chances of early-stage HER2-positive breast cancer recurrence and reduces the risk of death. A major study found that patients receiving trastuzumab had a 34% lower chance of cancer returning. This treatment has transformed breast cancer care by targeting cancer cells at their genetic level.

In this trial, some participants will receive paclitaxel and cyclophosphamide, chemotherapy drugs that stop cancer cells from growing and dividing. These drugs have successfully shrunk tumors before surgery. Using these treatments together could result in smaller tumors and possibly less invasive surgery. ^{1 2 6 7 8}

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 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]

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 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]

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 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]

Citations

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

Trastuzumab for early-stage, HER2-positive breast cancer Pooled analysis of all trials found a highly significant reduction in recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001; figure 1) and breast cancer mortality ...

2. herceptin.com herceptin.com/hcp/adjuvant-breast-cancer/efficacy/clinical-results.html

Herceptin Clinical Trial Results Review information on clinical studies for Herceptin® (trastuzumab) in HER2+ Adjuvant Breast Cancer. See Full Safety and Boxed Warnings for more ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822805

Long-Term Outcomes of Adjuvant Trastuzumab for 9 ... The findings suggest that 1 year vs 9 weeks of adjuvant trastuzumab is associated with improved disease-free survival after completed patient follow-up.

4. uclahealth.org uclahealth.org/news/release/25-years-herceptin-groundbreaking-advancement-breast-cancer

25 years of Herceptin: A groundbreaking advancement in ... Deemed as the “drug that changed the breast cancer treatment landscape,” Herceptin has saved millions of women's lives by targeting cancer at its genetic roots.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11178646/

Safety profile of trastuzumab deruxtecan in advanced breast ... The percentage of patients with a confirmed objective response among all patients was 52.3% (95% CI 47.1–57.4) in the T-DXd arm and 16.3% (95% CI: 11.3 to 22.5) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S096097762200042X

Safety and efficacy of adjuvant subcutaneous trastuzumab ... The 5-year disease-free survival rate was 87% for patients with early breast cancer. •. The no chemotherapy subgroup also had a similar 5-year disease-free ...

8. masseycancercenter.org masseycancercenter.org/news/targeted-treatment-herceptin-found-to-greatly-improve-longterm-survival-of-her2positive-breast-cance/

Targeted treatment Herceptin found to greatly improve long ... The study found that Herceptin, when added to chemotherapy, improved 10-year survival from 75 percent with chemotherapy alone to 84 percent with the addition ...