Gemcitabine + Trastuzumab + Pertuzumab for Breast Cancer

No longer recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Trastuzumab, Pertuzumab

Disqualifiers: Unstable angina, Myocardial infarction, CHF, 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: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs to determine if they can more effectively treat advanced breast cancer that tests positive for HER2, a protein that promotes cancer cell growth. The study combines gemcitabine, a standard chemotherapy drug, with trastuzumab and pertuzumab, which specifically target HER2. All three drugs have approval for treating breast cancer, but the trial aims to assess the effectiveness of using them together. Suitable candidates for this trial include those with advanced HER2-positive breast cancer who have previously been treated with trastuzumab and pertuzumab and have experienced cancer progression. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should have progression of disease on their current therapy, which might imply a change in treatment.

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

Research has shown that the combination of gemcitabine, trastuzumab, and pertuzumab has been tested for safety in people with breast cancer. Most patients in these studies found the treatment generally manageable. While many handled the treatment without serious side effects, some experienced issues like low blood cell counts, tiredness, and nausea.

All three drugs in this trial are already approved for treating metastatic breast cancer, indicating they have been tested and deemed safe for use in certain cases. However, this specific combination is still under study to ensure its effectiveness and safety for individuals who have undergone certain previous treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for breast cancer because it uses three powerful drugs: Gemcitabine, Trastuzumab, and Pertuzumab. Unlike standard treatments, which often focus on one target, this regimen combines chemotherapeutic and targeted therapies to attack cancer cells from multiple angles. Trastuzumab and Pertuzumab specifically target the HER2 protein, which is overexpressed in some breast cancers, while Gemcitabine disrupts the cancer cells' ability to replicate. This multi-pronged approach may offer more effective results, particularly for patients with HER2-positive breast cancer, by potentially overcoming resistance that can occur with single-agent therapies.

What evidence suggests that this combination of drugs could be effective for breast cancer?

This trial will evaluate the combination of gemcitabine, trastuzumab, and pertuzumab for treating breast cancer, particularly in cases involving the HER2 protein. Studies have shown that this drug combination can delay cancer progression by about 3 to 4 months. Trastuzumab and pertuzumab specifically target HER2-positive cancer cells and serve as standard treatments for advanced breast cancer. Previous studies have demonstrated that similar drug combinations can reduce the risk of death by 34% in some patients, suggesting potential benefits for those who have already received HER2-targeted therapy. ^{1 2 3 4 6}

Who Is on the Research Team?

Chau Dang, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage IV HER2-positive breast cancer who've had up to three prior chemotherapies in the metastatic setting and have previously been treated with trastuzumab + pertuzumab or pertuzumab-based therapy. Participants must have a good performance status, stable brain lesions if present, normal heart function, and acceptable blood counts and liver function. Pregnant individuals or those with severe past reactions to study drugs, hepatitis B/C, or recent serious heart issues cannot join.

Inclusion Criteria

My breast cancer is HER2 positive, confirmed by a lab test.

I am fully active and can carry on all my pre-disease activities without restriction.

I have been treated with trastuzumab and pertuzumab for my cancer.

Exclusion Criteria

I had a severe allergic reaction to trastuzumab or pertuzumab.

Pregnant patients

I have had hepatitis B or C in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine, trastuzumab, and pertuzumab intravenously. Gemcitabine is administered weekly on days 1 and 8 every 3 weeks, trastuzumab every 3 weeks or weekly, and pertuzumab every 3 weeks.

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment using progression-free survival and response criteria.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Pertuzumab
• Trastuzumab

Trial Overview The trial is testing a combination of gemcitabine (a standard chemotherapy drug) with two targeted therapies—trastuzumab (Herceptin) and pertuzumab (Perjeta)—to see how effective they are against advanced HER2-positive breast cancer after previous similar treatments. It's a Phase II study focusing on effectiveness as well as safety.

How Is the Trial Designed?

Group I: Gemcitabine, Trastuzumab, and Pertuzuma Experimental Treatment 3 Interventions

The regimen will consist of gemcitabine at 1000mg/m\^2 IV weekly days 1 + 8 q 3 weeks + trastuzumab every 3 weeks (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) + pertuzumab every 3 weeks (840 mg as a loading dose followed by 420 mg every 3 weeks), all given intravenously (IV). Trastuzumab may be given IV weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) in lieu of the every 3 week schedule. A loading dose of trastuzumab will not be required for patients who have received it \< 6 weeks prior to Cycle 1 Day 1.

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Hartford HealthCare

Collaborator

Trials

9

Recruited

1,300+

Published Research Related to This Trial

Pertuzumab is an effective anti-HER2 monoclonal antibody that works by preventing HER2 from forming heterodimers, which reduces tumor cell growth and survival, particularly in HER2-positive metastatic breast cancer.

In the phase III CLEOPATRA trial involving a combination of pertuzumab, trastuzumab, and docetaxel, patients experienced significantly improved progression-free survival and overall survival compared to those receiving placebo, with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer. McCormack, PL.[2021]

Pertuzumab, a new monoclonal antibody targeting HER2, has shown improved patient outcomes in clinical trials for early-stage and metastatic HER2-positive breast cancer, especially when used in combination with chemotherapy and trastuzumab.

The review highlights that while trastuzumab has improved survival for HER2-positive breast cancer, there is still a need for better treatment options, which pertuzumab aims to address, particularly for patients who continue to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. Lamond, NW., Younis, T.[2021]

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 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]

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]

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 266 patients with HER2-positive metastatic breast cancer, the majority received a treatment regimen of trastuzumab, pertuzumab, and a taxane, which aligns with the standard first-line therapy.

The median progression-free survival (PFS) for patients was 16.9 months, and the safety profile, including common side effects like fatigue and diarrhea, was consistent with findings from the pivotal CLEOPATRA trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes. Robert, NJ., Goertz, HP., Chopra, P., et al.[2020]

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

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31774522/

Efficacy and Safety of Gemcitabine With Trastuzumab and ... While continued use of trastuzumab in therapeutic combinations after disease progression is standard, the efficacy of continuing pertuzumab is unknown.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2755853

Gemcitabine With Trastuzumab and Pertuzumab Among ... Other trials have demonstrated median PFS of approximately 3 to 4 months for patients treated with trastuzumab and chemotherapy-based regimens ...

3. clinicaltrial.be clinicaltrial.be/en/details/11611?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Gemcitabine, Trastuzumab, and Pertuzumab in the ... The purpose of this study is to see if a combination of drugs can help to treat breast cancer. This is a Phase II study which will test ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4076842/

Overall survival benefit with pertuzumab, trastuzumab, and ... Treatment with pertuzumab plus trastuzumab plus docetaxel resulted in a 34% reduction in the risk of death during the course of the study (HR=0· ...

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.28_suppl.142

Safety and efficacy of gemcitabine and trastuzumab in ... Conclusions: The Combination Tmab and GEM is effective and well-tolerated regimen for patients previously treated with HER2-directed therapy, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6902832/

A Phase 2 Clinical Trial - PMC This phase 2 clinical trial demonstrated promising efficacy and confirmed the tolerability and safety profile of gemcitabine with trastuzumab ...