Paclitaxel + Trastuzumab + Pertuzumab for Breast Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Pregnancy, Infection, Hypertension, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—Paclitaxel, Trastuzumab, and Pertuzumab—to evaluate their effectiveness as a treatment for breast cancer. Researchers aim to determine if post-surgery treatments can be decided based on patients' responses to these drugs before surgery. The trial seeks participants with Stage II or III HER2-positive breast cancer, a specific type that these drugs target. Participants must not have received any prior treatment for their current breast cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking research.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot have received any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation, or experimental therapy.

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

Research has shown that the combination of paclitaxel, trastuzumab, and pertuzumab has been tested for safety in patients with HER2-positive breast cancer. In past studies, this combination was generally well-tolerated. The most common side effects resembled those of other cancer treatments and included tiredness, hair loss, and nausea.

Some reports noted more serious side effects, such as low white blood cell counts and diarrhea, but these were manageable with medical care. Pertuzumab, one of the drugs in this combination, has already received FDA approval for treating advanced breast cancer. This approval indicates the treatment is considered safe enough for use in those cases, though side effects can still occur.

Overall, while some side effects exist, earlier research suggests the treatment's safety is acceptable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Paclitaxel, Trastuzumab, and Pertuzumab for breast cancer because it targets HER2-positive cancer cells in a comprehensive way. Unlike standard treatments that might only block one pathway, this combination strikes at multiple points by using Trastuzumab and Pertuzumab to block the HER2 receptor, which is crucial for cancer cell growth. Meanwhile, Paclitaxel enhances the cancer-killing effects by disrupting cell division. This multi-pronged approach could potentially improve treatment effectiveness and outcomes for patients with HER2-positive breast cancer.

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

Research has shown that using paclitaxel, trastuzumab, and pertuzumab together holds promise for treating HER2-positive breast cancer. One study demonstrated a 56% pathologic complete response (pCR) rate with this combination, indicating that many patients showed no signs of cancer after treatment. This trial will evaluate the effectiveness of this combination further. Other studies have found that treatments targeting HER2, such as trastuzumab and pertuzumab, have significantly improved outcomes for breast cancer patients. These drugs target specific proteins on cancer cells, helping to stop the cancer from growing. Overall, evidence suggests this treatment combination effectively shrinks tumors and improves patient outcomes. ^{1 2 4 6 7}

Who Is on the Research Team?

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with Stage II or III HER2-positive invasive breast cancer, who can provide consent and tissue samples. They must have a tumor size of at least 1.5 cm, no serious heart conditions, an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), and acceptable blood test results. Pregnant/nursing individuals, those with unresolved infections or significant cardiovascular disease are excluded.

Inclusion Criteria

The study requires testing for estrogen receptor (ER) and progesterone receptor (PR) status.

I am willing to use birth control during the trial.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have received treatment for my current breast cancer.

I experience significant discomfort or pain from nerve damage.

I do not have any serious diseases that could affect my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive Paclitaxel, Trastuzumab, and Pertuzumab intravenously in 21-day cycles before surgery

12 weeks

3 visits (in-person) per cycle

Surgery and Evaluation

Participants undergo surgery and evaluation of pathologic complete response (pCR)

4 weeks

Adjuvant Treatment

Participants receive antibody doublet therapy in the adjuvant setting based on response to neoadjuvant treatment

2.5 years

Follow-up

Participants are monitored for recurrence-free interval (RFI), event-free survival (EFS), and overall survival (OS)

12 years

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The DAPHNe study tests if patients/doctors will choose post-surgery treatment based on pre-surgery response to a drug combo: Paclitaxel (Taxol), Trastuzumab (Herceptin), Pertuzumab (Perjeta). It also examines the collected blood/tissue from participants receiving these drugs for treating HER2-positive breast cancer.

How Is the Trial Designed?

Group I: Paclitaxel+Trastuzumab+Pertuzumab Experimental Treatment 3 Interventions

Paclitaxel is administered intravenously on days 1, 8, and 15 of each 21-day cycle Trastuzumab is administered intravenously on day 1 of each 21-day cycle Pertuzumab is administered intravenously on Day 1 of each 21-day cycle

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Terri Brodeur Breast Cancer Foundation

Collaborator

Trials

1

Recruited

100+

Susan G. Komen Breast Cancer Foundation

Collaborator

Trials

68

Recruited

220,000+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Published Research Related to This Trial

A comprehensive analysis of 14,707 adverse events related to pertuzumab from the FDA Adverse Event Reporting System revealed significant safety concerns, including potential risks of myelosuppression, cardiotoxicity, and other serious conditions occurring in 12 organ systems.

Most adverse events, particularly cardiac-related issues, were reported within the first month of therapy, highlighting the need for careful monitoring and preparedness for emergency interventions, especially in elderly patients and those with pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). Zou, SP., Yang, HY., Ouyang, ML., et al.[2023]

The novel anti-HER2 antibody 5G9 showed significantly stronger synergistic effects with trastuzumab in inhibiting cell growth compared to pertuzumab, achieving an 85% inhibition rate versus 55% (P<0.001).

In animal models, the combination of 5G9 and trastuzumab demonstrated greater antitumor efficacy than the pertuzumab and trastuzumab combination, suggesting that 5G9 could be a more effective treatment option for HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel HER2-targeting antibody 5G9 identified by large-scale trastuzumab-based screening exhibits potent synergistic antitumor activity. Ding, X., Gu, W., Zhong, Y., et al.[2021]

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 phase 3 trial involving 780 patients with HER2-positive metastatic gastric or gastro-oesophageal junction cancer, adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival compared to placebo, with median survival times of 17.5 months for the pertuzumab group and 14.2 months for the control group.

While serious adverse events were more common in the pertuzumab group (45%) compared to the control group (39%), no treatment-related deaths occurred in the pertuzumab group, suggesting a safety profile that warrants further investigation despite the lack of survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Tabernero, J., Hoff, PM., Shen, L., et al.[2023]

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 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]

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]

Citations

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Weekly paclitaxel with trastuzumab and pertuzumab in ... Outcomes of patients diagnosed with all stages of HER2-positive breast cancer have improved dramatically as therapies that specifically target HER2 have ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293757/

Real-World Outcomes of Adjuvant Paclitaxel and ... This multicenter, real-world study demonstrates that adjuvant trastuzumab and paclitaxel (TH) therapy provides excellent long-term outcomes in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0304383525003519

Efficacy and safety of inetetamab plus pertuzumab and nab ... Neoadjuvant treatment with inetetamab, in combination with pertuzumab and nab-paclitaxel, demonstrates good efficacy and tolerability, especially in ER- ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2804892

Efficacy of Endocrine Therapy Plus Trastuzumab and ... Treatment with paclitaxel plus trastuzumab and pertuzumab was associated with a superior pathological complete response (pCR) rate of 56% vs 24% after very ...

5. cancernetwork.com cancernetwork.com/view/nab-paclitaxel-combo-improves-response-vs-soc-in-her2-breast-cancer

Nab-Paclitaxel Combo Improves Response vs SOC in ... Nab-paclitaxel elicited a pathologic complete response rate of 66.3% compared with 57.6% with docetaxel plus carboplatin, the phase 3 HELEN-006 trial found.

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NCT03726879 | A Study To Evaluate the Efficacy and ... This study (also known as IMpassion050) will evaluate the efficacy and safety of atezolizumab compared with placebo when given in combination with neoadjuvant ...

7. perjeta-hcp.com perjeta-hcp.com/metastatic/efficacy.html

PERJETA® (pertuzumab) for HER2+ Metastatic Outcomes | HCP In the treatment of metastatic breast cancer, the most common adverse reactions (>30%) seen with PERJETA in combination with trastuzumab and docetaxel were ...