Paclitaxel + Trastuzumab + Pertuzumab for Inflammatory Breast Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, Lung disease, HIV, 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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for treating HER2-positive inflammatory breast cancer. The goal is to determine if adding pertuzumab, a targeted therapy, to the existing drugs paclitaxel (a chemotherapy drug) and trastuzumab (another targeted therapy) more effectively shrinks tumors before surgery and reduces the risk of cancer recurrence. Individuals diagnosed with HER2-positive inflammatory breast cancer who have not received prior breast cancer treatment might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other investigational or commercial cancer therapies. It's best to discuss your specific medications with the trial team.

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

Studies have shown that using paclitaxel, trastuzumab, and pertuzumab together can be safe for patients with HER2-positive breast cancer. Past research tested this combination in patients with advanced breast cancer, revealing manageable side effects. The FDA has approved pertuzumab, a medicine that targets cancer cells, for certain breast cancer cases.

Earlier trials demonstrated that adding pertuzumab to trastuzumab and chemotherapy improved outcomes and was generally well-tolerated. Side effects were usually mild to moderate, with some patients experiencing low blood cell counts and tiredness. These findings suggest that this combination is reasonably safe for further study in treating breast cancer before surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Paclitaxel, Trastuzumab, and Pertuzumab for treating inflammatory breast cancer because it offers a comprehensive approach targeting the cancer cells more effectively. Unlike standard treatments that might use these drugs sequentially, this approach uses them together, maximizing their cancer-fighting potential. Paclitaxel disrupts cell division, while Trastuzumab and Pertuzumab both target the HER2 protein on cancer cells, but in slightly different ways, enhancing the overall impact. This combination aims to shrink tumors more efficiently before surgery, potentially improving outcomes for patients with this aggressive cancer type.

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

Research has shown that using pertuzumab with trastuzumab and paclitaxel may help treat HER2-positive breast cancer. In this trial, participants will receive a combination of these drugs. Studies have found that adding pertuzumab to trastuzumab and chemotherapy can lead to better outcomes for patients with advanced breast cancer. Specifically, this combination has improved survival rates and reduced the risk of cancer recurrence. Pertuzumab and trastuzumab work together to block the HER2 protein, stopping cancer cells from growing. This treatment is effective because it targets cancer cells more precisely. Overall, this approach has improved the chances of beating the cancer and preventing its return. ^{1 3 4 5 6}

Who Is on the Research Team?

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with inflammatory breast cancer that's HER2 positive and haven't had prior breast cancer treatment. Participants must be willing to undergo a biopsy, not have metastatic cancer in organs or bones (though nodal involvement is okay), and can't be pregnant, breastfeeding, or have certain other cancers unless they've been disease-free for 5 years.

Inclusion Criteria

I have been diagnosed with inflammatory breast cancer.

I am willing to have a biopsy of my affected breast for research.

My cancer has not spread to my organs or bones, but may be in many lymph nodes.

Exclusion Criteria

I have cancer that has spread to my brain.

I have trouble breathing even when I'm resting due to lung disease or cancer.

I have received treatment for breast cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preoperative Treatment

Participants receive trastuzumab and pertuzumab, followed by paclitaxel for 16 weeks

16 weeks

Weekly visits for infusions

Surgery

Participants undergo surgery for removal of breast cancer approximately 4-5 weeks after last paclitaxel infusion

4-5 weeks post-treatment

Postoperative Treatment

Participants receive either AC chemotherapy or continue trastuzumab and pertuzumab to complete 12 months of HER2-directed therapy

12 months

Every 3 weeks for infusions

Radiation Therapy

Radiation therapy to the mastectomy site and surrounding lymph nodes, administered daily for 6-7 weeks

6-7 weeks

Daily visits, Monday through Friday

Follow-up

Participants are monitored for long-term side effects and cancer recurrence, with regular follow-up visits planned for up to 13 years

Up to 13 years

Every 3 months for the first year, every 6 months for the next 4 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The study tests the combination of paclitaxel, trastuzumab, and pertuzumab as preoperative therapy for inflammatory breast cancer. Pertuzumab is investigational in this context. The goal is to see if this combo reduces the chance of recurrence and helps patients proceed to mastectomy.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 7 Interventions

Run in: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1 Week 1) Pre-Op: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8 Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above, add Pertuzumab 420 mg IV x 3 weeks. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued x 3 weeks until surgery Modified Radical Mastectomy Post-Op: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV x 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg x 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation to the chest wall / regional lymph nodes and endocrine therapy by standard of care.

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+

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]

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 phase IIa study involving 30 patients with advanced gastric cancer, the combination of pertuzumab and trastuzumab showed a well-tolerated safety profile, with partial responses in 86% of patients receiving a specific dosing regimen.

The pharmacokinetics indicated that the serum concentration of pertuzumab was lower in this gastric cancer population compared to those with metastatic breast cancer, leading to the selection of the 840 mg q3w dose for further phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Kang, YK., Rha, SY., Tassone, P., et al.[2021]

In a study of 106 patients with HER2-positive metastatic breast cancer, the combination of pertuzumab, trastuzumab, and vinorelbine achieved a high objective response rate of 74.2%, indicating strong efficacy as a first-line treatment option.

The treatment was generally well tolerated, with common side effects including diarrhea and neutropenia, but no unexpected toxicities or confirmed cases of congestive heart failure, suggesting it is a safe alternative for patients unable to receive standard docetaxel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results. Perez, EA., López-Vega, JM., Petit, T., et al.[2018]

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 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 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]

Citations

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

Real-World Outcomes of Adjuvant Paclitaxel and ... Although intensive treatments have significantly improved survival rates, patients with smaller tumors and no lymph node involvement might not ...

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

Efficacy and safety of inetetamab plus pertuzumab and nab ... Inetetamab plus pertuzumab and nab-paclitaxel neoadjuvant therapy achieves 56.5% tpCR with manageable safety in HER2+ BC.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01730833

NCT01730833 | Pertuzumab, Trastuzumab, and Paclitaxel ... This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel albumin-stabilized nanoparticle formulation work in treating patients with human ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1703643

Adjuvant Pertuzumab and Trastuzumab in Early HER2 ... A 3-year rate of invasive-disease–free survival of 89.2% was assumed for the placebo group, on the basis of the results of the Breast Cancer International ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5017157/

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 ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03716180/

Clinical Trial - Breast Cancer: HER2 Positive In addition, the investigators are evaluating how the body's immune system works with paclitaxel, trastuzumab, and pertuzumab to kill cancer ...