Chemotherapy + Targeted Therapy for Breast Cancer

Overseen By UC Irvine Health Chao Family Comprehensive Cancer Center

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Disqualifiers: Metastasis, Heart failure, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 54

Duration: 12 weeks

120 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 coordinators or your doctor.

What data supports the effectiveness of the drug combination of Bevacizumab, Avastin, Carboplatin, Paraplatin, Carboplatinum, Paclitaxel, Taxol, Onxol, Abraxane, Paclitaxel, Pertuzumab, Perjeta, Trastuzumab, Herceptin, Trazimera, Herzuma, Ontruzant for breast cancer?

Research shows that adding pertuzumab to trastuzumab and chemotherapy can improve survival rates in HER2-positive breast cancer. Additionally, combining bevacizumab with a taxane like paclitaxel has been shown to improve progression-free survival in metastatic breast cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy and targeted therapy for breast cancer generally safe?

The combination of trastuzumab and pertuzumab with chemotherapy has been studied for breast cancer, and while it can improve treatment outcomes, it may increase toxicity. Cardiac safety data is limited, but some studies suggest it can be used safely with radiation therapy without excess risk of toxicity. ^{1 2 6 7 8}

What makes the combination of Bevacizumab, Carboplatin, Paclitaxel, Pertuzumab, and Trastuzumab unique for breast cancer treatment?

This treatment is unique because it combines targeted therapies like trastuzumab and pertuzumab, which specifically attack HER2-positive breast cancer cells, with chemotherapy agents like paclitaxel and carboplatin, and includes bevacizumab, an antiangiogenic drug that cuts off the blood supply to tumors, potentially enhancing the overall effectiveness against HER2-positive breast cancer. ^{1 4 9 10 11}

What is the purpose of this trial?

The purpose of this phase II is to study the efficacy and toxicity of carboplatin and paclitaxel with pertuzumab and trastuzumab in HER2 positive and carboplatin and paclitaxel with bevacizumab in HER2 negative in the neoadjuvant setting for the treatment of breast cancer.

Research Team

Rita Mehta, MD

Principal Investigator

University of California, Irvine

Eligibility Criteria

This trial is for women over 18 with breast cancer, who have a performance status of 0-2 and normal heart function. HER2 positive patients receive carboplatin, paclitaxel, pertuzumab, and trastuzumab; HER2 negative get bevacizumab instead. Exclusions include men, pregnant/nursing women not using contraception, unhealed wounds, allergies to treatments, significant heart conditions or bleeding risks.

Inclusion Criteria

- Your blood counts need to be in a certain range. - Your liver and kidney function tests need to be within normal limits. - Women capable of getting pregnant need to have a negative pregnancy test within 14 days before starting the trial.

I am a woman aged 18 or older.

I know my cancer's HER2 status.

Exclusion Criteria

I have a serious heart condition, such as heart failure or angina.

I am not pregnant or nursing and agree to use contraception during and for a month after treatment.

My blood counts are low, increasing my risk for severe bleeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly Carboplatin and Paclitaxel with either Trastuzumab and Pertuzumab for HER2-positive patients or Bevacizumab for HER2-negative patients in the neoadjuvant setting

12 weeks

Weekly visits for 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Visits up to 42 days after treatment

Long-term follow-up

Participants are monitored for progression-free survival and complete response rates

2 years

Treatment Details

Interventions

• Bevacizumab
• Carboplatin
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The study tests the effectiveness and safety of combining chemotherapy drugs (carboplatin and paclitaxel) with targeted therapies (pertuzumab and trastuzumab for HER2 positive or bevacizumab for HER2 negative) in treating early-stage breast cancer before surgery.

Participant Groups

Group I: Carboplatin+Paclitaxel+Trastuzumab+Pertuzumab (HER2+) Experimental Treatment 4 Interventions

Carboplatin weekly 12 doses Paclitaxel weekly 12 doses Trastuzumab weekly 12 doses Pertuzumab every 3 weeks, 4 doses

Group II: Carboplatin+Paclitaxel+Bevacizumab (HER2-) Experimental Treatment 3 Interventions

Carboplatin weekly 12 doses Paclitaxel weekly 12 doses Bevacizumab every other week, 5 doses

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Findings from Research

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 the TRAIN-2 study involving 110 patients with HER2-positive breast cancer, the addition of pertuzumab to chemotherapy regimens resulted in neutropenia as the most common hematologic toxicity, affecting 53% of patients in the FEC-T arm and 51% in the PTC arm.

While both regimens showed manageable toxicity, the FEC-T arm had a higher incidence of asymptomatic ejection fraction decrease (24%) compared to the PTC arm (11%), and diarrhea was more common in the PTC arm (18% vs. 5%), indicating different toxicity profiles depending on the chemotherapy backbone used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study. van Ramshorst, MS., van Werkhoven, E., Honkoop, AH., et al.[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 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]

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

In a study of 55 women with HER2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab with chemotherapy resulted in a median progression-free survival (PFS) of 10 months, indicating significant efficacy in this treatment approach.

The treatment was generally safe, with common side effects including neutropenia (40%), leukopenia (34.5%), and thrombocytopenia (32.7%), but serious adverse reactions were relatively low, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab plus pertuzumab in combination with chemotherapy in metastatic HER2-positive breast cancer: a retrospective single-armed cohort study in China. Qian, Y., Peng, Y., Zhou, H., et al.[2022]

Standard treatments for breast cancer after initial chemotherapy include capecitabine, S-1, vinorelbine, irinotecan, or gemcitabine, which are effective options for managing the disease.

Newer therapies like lapatinib for trastuzumab-resistant cases and combinations like bevacizumab with taxanes show promise, highlighting the need for further research on optimal drug sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab]. Ito, Y., Kobayashi, K.[2016]

References

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. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study. [2022]

3. France pubmed.ncbi.nlm.nih.gov

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

4. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of late line pertuzumab with trastuzumab and chemotherapy in HER2-positive metastatic breast cancer: An Australian case series. [2020]

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

A Phase II study of bevacizumab in combination with trastuzumab and docetaxel in HER2 positive metastatic breast cancer. [2022]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. [2023]

8. China pubmed.ncbi.nlm.nih.gov

Trastuzumab plus pertuzumab in combination with chemotherapy in metastatic HER2-positive breast cancer: a retrospective single-armed cohort study in China. [2022]

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

New treatment strategies for human epidermal growth factor receptor 2-positive breast cancer in 2023. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for breast cancer refractory to anthracycline, taxane or trastuzumab]. [2016]

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]