Chemotherapy +/− Trastuzumab for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Prior malignancy, Invasive breast carcinoma, 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: 6

Duration: 18 weeks

121 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. 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. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer. PURPOSE: This randomized phase II trial is comparing two different regimens of combination chemotherapy given together with or without trastuzumab to see how well they work in treating patients with stage II or stage III breast cancer.

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, it does mention that you should not have had antiestrogen treatment for breast cancer prevention in the past 5 years.

What data supports the effectiveness of the drug combination of chemotherapy and trastuzumab for breast cancer?

Research shows that adding trastuzumab to chemotherapy improves response and survival rates in patients with HER2-positive breast cancer. A study found that a combination of paclitaxel, carboplatin, and trastuzumab was highly effective, with 44% of patients achieving complete response in both breast and lymph nodes. ^{1 2 3 4 5}

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

The combination of chemotherapy drugs like docetaxel, carboplatin, and trastuzumab is generally considered safe for treating HER2-positive breast cancer, but it can cause significant side effects such as neutropenia (low white blood cell count) and fatigue. Using colony-stimulating factors can help reduce some of these side effects. Cardiac safety is generally good, with no severe heart-related issues reported in the studies. ^{6 7 8 9 10}

How is the drug combination of chemotherapy and trastuzumab unique for breast cancer treatment?

This treatment is unique because it combines trastuzumab, a targeted therapy that specifically attacks HER2-positive breast cancer cells, with chemotherapy drugs, enhancing the effectiveness of the treatment and improving survival rates compared to chemotherapy alone. The combination is particularly effective in HER2-positive breast cancer, offering a synergistic effect that improves outcomes while maintaining a manageable side effect profile. ^{1 3 4 11 12}

Research Team

Joanne Mortimer, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with stage II or III breast cancer, who have not had chest radiotherapy or other cancers in the past 5 years. They must have good organ function and performance status, no significant neuropathy, and if fertile, agree to use nonhormonal contraception.

Inclusion Criteria

I have inflammatory breast cancer.

Absolute neutrophil count ≥ 1,500/mm^3

Not pregnant or nursing

Exclusion Criteria

I haven't had cancer in the past 5 years, except for certain skin cancers or early-stage cervical cancer.

I had a non-spreading breast cancer diagnosis within the last 5 years.

I haven't taken hormone therapy for conditions other than preventing breast cancer in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy with or without trastuzumab, depending on HER2/neu status

18 weeks

6 visits (in-person) for Arm I; 7 visits (in-person) for Arm II and III

Surgery

Participants undergo surgery to remove the tumor within 4 weeks after completion of chemotherapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Carboplatin, Paclitaxel, Docetaxel, Cyclophosphamide, Doxorubicin Hydrochloride
• Trastuzumab

Trial Overview The study is testing how well combination chemotherapy works with or without trastuzumab (a monoclonal antibody) in shrinking tumors before surgery. Patients are randomly assigned to receive either just chemo or chemo plus trastuzumab.

Participant Groups

Group I: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and trastuzumab Experimental Treatment 5 Interventions

Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin.

Group II: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin Experimental Treatment 4 Interventions

Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses.

Group III: Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide Active Control 3 Interventions

Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancer significantly improves patient outcomes, providing an additional 0.84 quality-adjusted life years (QALY) and 1.16 life years gained (LYG) compared to chemotherapy without trastuzumab.

The cost-effectiveness analysis indicates that trastuzumab therapy has an incremental cost-effectiveness ratio (ICER) of approximately US$19,599.26 per QALY and US$14,180.68 per LYG, suggesting it may be considered cost-effective in Brazil under specific economic thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil. Botelho, CH., Estevez-Diz, MDP., Campolina, AG.[2022]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

In a study of 95 patients receiving the TCH regimen for Her2-positive breast cancer, the use of primary prophylaxis (PP) with colony-stimulating factors significantly reduced severe hematological toxicities like neutropenia and leukopenia compared to those who did not receive PP.

Despite higher overall toxicity rates compared to earlier studies, the TCH regimen showed high effectiveness with a disease-free survival (DFS) rate of 98.9% and overall survival (OS) rate of 100% after a mean follow-up of 22.9 months, supporting the recommendation for routine use of PP to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of docetaxel, carboplatin, and trastuzumab combination as adjuvant or neo-adjuvant treatment for Her2 positive breast cancer patients and impact of colony-stimulating factor prophylaxis. Bayo, J., Aviñó, V., Toscano, F., et al.[2022]

In a study of 81 HER2-positive breast cancer patients, the docetaxel + trastuzumab + pertuzumab regimen achieved a slightly higher complete pathological remission rate (51.2%) compared to the docetaxel + carboplatin + trastuzumab + pertuzumab regimen (44.7%).

The docetaxel + carboplatin regimen was associated with significantly higher rates of severe toxicity (68.4% vs 39.5%) and more frequent adjustments to the treatment plan, indicating that it may be less tolerated than the docetaxel + trastuzumab + pertuzumab regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dual Anti-HER2 Blockade and Docetaxel With or Without Carboplatin as Neoadjuvant Regimen for Treatment of HER2-Positive Breast Cancer. Lin, B., Fan, J., Liu, F., 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]

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]

References

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

Ongoing and planned adjuvant trials with trastuzumab. [2015]

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

Paclitaxel, carboplatin, and trastuzumab in a neo-adjuvant regimen for HER2-positive breast cancer. [2015]

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

Rationale for trastuzumab (Herceptin) in adjuvant breast cancer trials. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

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

Toxicity of docetaxel, carboplatin, and trastuzumab combination as adjuvant or neo-adjuvant treatment for Her2 positive breast cancer patients and impact of colony-stimulating factor prophylaxis. [2022]

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

Efficacy and Safety of Dual Anti-HER2 Blockade and Docetaxel With or Without Carboplatin as Neoadjuvant Regimen for Treatment of HER2-Positive Breast Cancer. [2023]

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

Phase II trial of weekly docetaxel, vinorelbine, and trastuzumab in the first-line treatment of patients with HER2-positive metastatic breast cancer. [2018]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety and tolerability of docetaxel, cyclophosphamide, and trastuzumab compared to standard trastuzumab-based chemotherapy regimens for early-stage human epidermal growth factor receptor 2-positive breast cancer. [2020]

10. 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]

11. 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]

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

Maximizing clinical benefit with trastuzumab. [2019]