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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether combining chemotherapy drugs with or without trastuzumab is more effective for treating stage II or III breast cancer. Trastuzumab, a monoclonal antibody, may help stop tumor growth. Participants will receive various combinations of chemotherapy drugs, with some also receiving trastuzumab, to identify the most effective combination. This trial may suit individuals with stage II or III invasive breast cancer who haven't recently undergone chest radiation or certain other treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that the combination of drugs used in this trial has been studied before. Doxorubicin, cyclophosphamide, paclitaxel, and carboplatin are common chemotherapy drugs. They usually cause side effects like nausea, tiredness, and hair loss, but are generally well-tolerated.

Adding trastuzumab, also known as Herceptin®, can enhance the treatment's effectiveness for certain types of breast cancer. However, trastuzumab may cause heart-related side effects. Studies have found that patients taking trastuzumab may experience heart problems, especially when combined with drugs like doxorubicin. Monitoring heart health during treatment is crucial.

Overall, these treatments have been used in many patients and are known to have manageable side effects. However, as with any treatment, there is always a balance between benefits and risks. Participants in the trial should be aware of these potential side effects and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they explore combining standard chemotherapy with trastuzumab, a targeted therapy known for its effectiveness in HER2-positive breast cancer. Unlike traditional chemotherapy alone, which attacks all rapidly dividing cells, trastuzumab specifically targets the HER2 protein, which can promote the growth of cancer cells. This targeted approach could potentially enhance treatment effectiveness with fewer side effects. Additionally, the study evaluates different combinations of chemotherapy drugs, like paclitaxel and carboplatin, to optimize treatment regimens for better patient outcomes.

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

Research has shown that the chemotherapy drugs doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and carboplatin are used together to treat breast cancer. In this trial, one group will receive doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel and carboplatin. However, adding carboplatin has not significantly improved overall survival rates. Another group will receive the same chemotherapy regimen with the addition of trastuzumab. Trastuzumab, known for its effectiveness in treating HER2-positive breast cancer, greatly reduces the chances of cancer recurrence and lowers death rates. When combined with chemotherapy, trastuzumab enhances the treatment's effectiveness, especially for early-stage breast cancer. Thus, trastuzumab is a valuable addition to chemotherapy for some breast cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Joanne Mortimer, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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

Bilirubin normal (except for patients with Gilbert's disease)

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02488967

Study Details | NCT02488967 | Doxorubicin Hydrochloride ... This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin work in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5865448/

Neoadjuvant Chemotherapy Considerations in Triple ... Overall survival (OS) differences were also not significant, with 81.9% OS in the carboplatin group versus 84.6% without carboplatin (HR, 1.15; ...

3. ctv.veeva.com ctv.veeva.com/study/doxorubicin-hydrochloride-and-cyclophosphamide-followed-by-paclitaxel-with-or-without-carboplatin-in

Doxorubicin Hydrochloride and Cyclophosphamide Followed ... This randomized phase III trial studies how well doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/17588359221085556

Chemotherapy regimen choice and patient outcomes in ... We sought to evaluate outcomes in patients with early TNBC treated with ABRs versus those treated with anthracycline-sparing regimens (ASRs).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7901219/

Cost-effectiveness of paclitaxel, doxorubicin ... - PubMed Central This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00295893?tab=results

Combination Chemotherapy With or Without Trastuzumab ... Patients receive 60 mg/m2 doxorubicin hydrochloride IV and 600 mg/m2 cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4048960/

Cardiac Safety Analysis of Doxorubicin and ... To assess cardiac safety and potential cardiac risk factors associated with trastuzumab in the NCCTG N9831 Intergroup adjuvant breast cancer trial.

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

Herceptin Clinical Trial Results Doxorubicin and cyclophosphamide plus paclitaxel with or without trastuzumab in treating women with node-positive breast cancer that overexpresses HER2.

9. sciencedirect.com sciencedirect.com/science/article/pii/S193652332500083X

Cardiotoxicity of breast cancer drug treatments Some breast cancer therapies increase cardiotoxicity/cardiovascular complication risk. Mechanisms include blockage of HER2 which has underlying ...

10. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1233-1

Safety, activity, and molecular heterogeneity following ... Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER2-positive metastatic breast cancer.