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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of combining chemotherapy and targeted therapies for breast cancer treatment. It examines different drug combinations based on whether the cancer is HER2 positive or HER2 negative. Individuals with breast cancer that is at least 1 cm in size or has spread to nearby lymph nodes, and who know their HER2 status, might be suitable candidates. Participants will receive a mix of drugs, such as carboplatin and paclitaxel, to evaluate their combined effectiveness in shrinking the tumor before surgery. As a Phase 2 trial, this research measures the treatment's effectiveness 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. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the combination of carboplatin, paclitaxel, and bevacizumab is generally well-tolerated in patients with HER2-negative breast cancer. One study found that adding bevacizumab to paclitaxel helped patients delay cancer progression, although it did not extend overall lifespan. Common side effects included high blood pressure and nosebleeds, but these were manageable.

For patients with HER2-positive breast cancer, using carboplatin, paclitaxel, trastuzumab, and pertuzumab together has shown promising results. Previous patients experienced benefits in slowing cancer growth. These treatments are also approved for other types of breast cancer, indicating general safety. Side effects often include diarrhea and tiredness, but these are usually controllable.

Both treatment combinations have been studied before, providing some confidence in their safety. However, side effects can vary. It is important to discuss potential risks and benefits with a healthcare provider before deciding to join a trial. ^{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 combine chemotherapy with targeted therapies to potentially enhance effectiveness. Unlike traditional chemotherapy, which broadly attacks fast-growing cells, the combination of Carboplatin and Paclitaxel with Bevacizumab targets blood vessel growth in HER2-negative breast cancer, potentially reducing tumor blood supply. On the other hand, in HER2-positive cases, adding Trastuzumab and Pertuzumab to the mix focuses on blocking HER2 receptors, which are often overexpressed in this breast cancer subtype, thereby inhibiting tumor growth more precisely. These innovative combinations could lead to more personalized and potentially more effective treatment options for patients.

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

In this trial, participants with HER2-negative breast cancer will receive a combination of carboplatin, paclitaxel, and bevacizumab. Research has shown mixed results for this combination in treating HER2-negative breast cancer. Bevacizumab can delay cancer progression but does not extend survival. However, adding carboplatin has effectively shrunk cancer in the breast and lymph nodes.

For participants with HER2-positive breast cancer, the trial will test a combination of trastuzumab, pertuzumab, carboplatin, and paclitaxel. Studies have found that this combination extends survival and significantly delays cancer progression. The FDA has approved the use of pertuzumab and trastuzumab together for early HER2-positive breast cancer, supporting their effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Rita Mehta, MD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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