Anti-HER2 Therapy for Breast Cancer

Not yet recruiting at 4 trial locations

Overseen By Olufunmilayo Olopade

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Hormone therapy

Must not be taking: Tamoxifen, Raloxifene

Disqualifiers: Metastasis, Uncontrolled infection, Heart failure, 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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a treatment specifically designed for Nigerian women with a type of breast cancer that tests positive for the HER2 protein. The researchers aim to determine the effectiveness and safety of treating this cancer with medications like pertuzumab and trastuzumab emtansine (also known as Kadcyla), both before and after surgery. The trial includes different groups for women whose cancer can or cannot be operated on, to assess how their cancer responds to the treatment. Suitable candidates have a HER2-positive breast tumor at least 2 cm in size, have not received prior chemotherapy for breast cancer, and can undergo a core needle biopsy. As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you have not received more than 4 weeks of tamoxifen therapy for this cancer. If you have been on tamoxifen or raloxifene for prevention, you must stop at least one month before joining the study.

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

Research has shown that pertuzumab and trastuzumab emtansine, both used to treat HER2-positive breast cancer, have been safe in past studies. Pertuzumab, when combined with other treatments, reduced the risk of death by 17% for patients with early-stage breast cancer, indicating both safety and effectiveness.

For trastuzumab emtansine, studies have found it effective, with generally manageable side effects for patients with advanced HER2-positive breast cancer. Some patients reported mild issues like nerve damage and changes in liver function, but these are uncommon and manageable.

Both treatments have FDA approval for certain conditions, indicating they have passed strict safety tests. While this trial targets a specific group, previous research provides a reassuring background for their use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using pertuzumab and trastuzumab emtansine for breast cancer treatment because they specifically target the HER2 protein, which is overexpressed in certain types of breast cancer. Unlike traditional chemotherapy that attacks all rapidly dividing cells, these drugs focus on cancer cells with high HER2 levels, potentially reducing damage to healthy cells. Additionally, the combination of these drugs with standard treatments like docetaxel offers a tailored approach based on how the cancer responds, which can be more effective for individual patients. This personalized treatment strategy is a significant advancement over conventional methods, which do not always consider specific cancer characteristics.

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

Research has shown that trastuzumab emtansine, a treatment in this trial for HER2-positive breast cancer, significantly improves both progression-free survival and overall survival compared to other treatments. In one study, 75.7% of patients responded well, with some showing no signs of cancer. Pertuzumab, another treatment option in this trial, slows cancer growth and increases survival rates when combined with other therapies. It lowered the risk of death by 17% for patients with early-stage HER2-positive breast cancer. Trastuzumab alone has been proven to significantly reduce the chance of cancer recurrence and increase survival rates for early-stage HER2-positive breast cancer. Together, these treatments have shown promising results in effectively managing HER2-positive breast cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Olufunmilayo Olopade, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for Nigerian women with a type of breast cancer that tests positive for HER2, which means the cancer grows in response to a certain protein. Participants should be preparing for or have completed surgery and are now considering further treatment.

Inclusion Criteria

I am a woman aged between 18 and 70.

Written informed consent must be obtained prior to any screening procedures

Required Initial Laboratory Data: Adequate hematologic, renal, and hepatic function as defined by specific criteria

Exclusion Criteria

I take medication for chest pain.

Participation in any investigational drug study within 4 weeks preceding the start of study treatment

My cancer has spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

All participants receive a combination of docetaxel, trastuzumab, and pertuzumab for 18 weeks

18 weeks

Every 3 weeks

Phase 2 Treatment - Operable

Participants undergo surgery and continue to receive pertuzumab and trastuzumab for 36 weeks, with optional hormone therapy

36 weeks

Phase 2 Treatment - Inoperable

Participants receive trastuzumab emtansine plus standard chemotherapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Pertuzumab
• Trastuzumab emtansine

Trial Overview

The study is testing how effective and safe anti-HER2 therapies like Tamoxifen, Docetaxel, Goserelin, Trastuzumab emtansine, Letrozole, and Pertuzumab Injection are when given before and after surgery to treat HER2+ breast cancer.

How Is the Trial Designed?

Group I: Phase 2 - Operable (participants who are able to have surgery) Experimental Treatment 6 Interventions

Participants in this group will have breast cancer that shows a complete or incomplete response (as assessed by ultrasound) to the study drug combination given in phase 1 of study. Based on how their breast cancer responds to the phase 1 study drugs, participants in this group will: \- undergo surgery and will continue to receive pertuzumab (600 mg) and trastuzumab (600 mg) for 36 weeks. Participants may also receive hormone therapy (as recommended by study doctor) based on status of breast cancer. This drug will be given as an injection under the skin. Some participants in this group may also receive tamoxifen (as an oral tablet; 20 mg daily for 10 years after surgery), letrozole (as an oral tablet 2.5 mg daily for 10 years after surgery) and/or goserelin (hormone injection 10.8 mg every 1-3 months) based on their human epidermal growth factor receptor 2 (HER2) status as assessed by the treating doctor.

Group II: Phase 2 - Inoperable (participants who are not able to have surgery) Experimental Treatment 1 Intervention

Participants in this group will have breast cancer that shows a partial response (as assessed by ultrasound) to the study drugs given in phase 1 or their breast cancer stayed the same or got worse after receiving study drugs during phase 1. Based on how their breast cancer responds to the phase 1 study drug regimen, participants in this group will receive trastuzumab emtansine (intravenously) plus standard chemotherapy as recommended by their doctor.

Group III: Phase 1: All Participants Experimental Treatment 3 Interventions

All participants will receive a combination of: * docetaxel (starting dose - 75 mg/m2), increasing to 100mg/m2 by cycle 2 (if tolerated) for 4-6 cycles (for a total of 18 weeks). Docetaxel will be give as an injection. * trastuzumab and pertuzumab (loading dose of 1200 mg of pertuzumab and 600 mg trastuzumab) for 52 weeks followed by 600 mg pertuzumab and 600 mg trastuzumab every 3 weeks for 15 cycles (for a total of 52 weeks). These two drugs will be given as subcutaneous injections under the skin.

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

Approved in European Union as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in United States as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Canada as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Japan as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a review of six studies involving 996 patients with HER2-positive breast cancer, the addition of pertuzumab to trastuzumab emtansine (T-DM1) ± taxane did not significantly improve objective response or clinical benefit rates compared to T-DM1 alone.

While the combination treatment was associated with increased risks of certain adverse events like diarrhea and rash, it also showed a decreased risk of thrombocytopenia, indicating a complex safety profile that requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. Zhang, J., Li, J., Zhu, C., et al.[2022]

In a study of 325 HER2-positive metastatic breast cancer patients, the objective response rate (ORR) for treatments following trastuzumab emtansine (T-DM1) was 22.8%, indicating limited effectiveness of post-T-DM1 therapies.

The median overall survival (OS) for patients after T-DM1 was 23.7 months, suggesting that while some patients may benefit, there is a need for further research into more effective treatment options beyond T-DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B). Yokoe, T., Kurozumi, S., Nozawa, K., et al.[2021]

Trastuzumab emtansine (T-DM1) can cause lacrimal drainage system stenosis, leading to excessive tearing in patients, as seen in a case study of a 36-year-old woman with metastatic breast cancer.

The condition was successfully treated with a topical steroid (dexamethasone), demonstrating that while T-DM1 is effective for HER2-positive breast cancer, it can have side effects that are manageable with appropriate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. Kim, CY., Kim, N., Choung, HK., et al.[2020]

In T-DM1-resistant HER2-positive breast cancer cells, the combination of trastuzumab and pertuzumab (TRAS + PER) showed enhanced antitumor effects, significantly inhibiting cell proliferation and inducing apoptosis compared to either drug alone.

The study demonstrated that TRAS + PER effectively suppressed tumor growth in a xenograft model of T-DM1-resistant cancer, suggesting it could be a promising treatment option for patients who develop resistance to T-DM1 while maintaining HER2 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. Yamashita-Kashima, Y., Shu, S., Osada, M., et al.[2021]

In the phase 3 MARIANNE trial involving 1095 patients with HER2-positive advanced breast cancer, trastuzumab emtansine (T-DM1) demonstrated similar overall survival rates compared to trastuzumab plus a taxane, while showing better tolerability and fewer severe side effects.

Patients receiving T-DM1 had a longer median overall survival when they achieved an objective tumor response, indicating that T-DM1 is a viable first-line treatment option for those unsuitable for taxane-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: Final results from MARIANNE. Perez, EA., Barrios, C., Eiermann, W., et al.[2020]

Ado-trastuzumab emtansine (T-DM1) is effective for treating HER2-positive breast cancers, but this case report highlights a serious risk of fatal pulmonary toxicity, specifically acute eosinophilic pneumonia, associated with its use.

The patient had previously received two HER2-targeted therapies, suggesting that prior treatments may contribute to the risk of additive toxicity when using T-DM1, indicating the need for careful monitoring in patients undergoing multiple lines of HER2-targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab. LaMorte, D., Desmond, D., Ellis, J., et al.[2023]

Trastuzumab emtansine (T-DM1) has shown a favorable safety profile in 884 patients with HER2-positive metastatic breast cancer, with most adverse events being manageable and asymptomatic, such as fatigue and nausea.

The treatment demonstrated superior efficacy compared to standard therapies in previous studies, making T-DM1 a promising option for further exploration in other breast cancer settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. Diéras, V., Harbeck, N., Budd, GT., et al.[2019]

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