Combination Therapy for Breast Cancer

Recruiting at 4 trial locations

Overseen By Rita Vaccaro, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: GnRH agonists

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: HER2 negative, Uncontrolled brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, phase I/II trial of anastrozole, palbociclib, trastuzumab, and pertuzumab is proposed as first-line therapy in metastatic hormone receptor-positive, HER2-positive breast cancer patients. In this phase I/II clinical trial, the researchers aim to establish the safety and efficacy of dual HER2 therapy in combination with palbociclib and anastrozole, which represents a novel and all biologic approach to the treatment of HR+, HER2+ metastatic breast cancer. Additionally, the researchers aim to examine potential biomarkers of response to palbociclib including cyclin D1, cyclin E1 and cyclin E2 expression levels, CDK 2, 4, and 6 levels, phosphorylated retinoblastoma expression and p16 levels. The researchers intend to use RNA sequencing to assess for other predictors of response in an unbiased manner to see if this correlates with inhibition of Ki-67 and phosphorylated retinoblastoma expression as well as evaluate for potential mechanisms of resistance.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs that interact with the study drugs, like strong CYP3A4 inducers or inhibitors. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination therapy for breast cancer?

Research shows that adding pertuzumab to trastuzumab and chemotherapy can improve survival rates in women with HER2-positive breast cancer. This combination has been shown to increase progression-free survival and overall survival, making it a valuable addition to breast cancer treatment. ^{1 2 3 4 5}

Is the combination therapy for breast cancer safe for humans?

The combination of trastuzumab and pertuzumab, often used in treating HER2-positive breast cancer, has been shown to be safe in clinical trials, with no excess risk of toxicity when combined with radiation therapy. However, caution is advised when combining these therapies with certain other treatments, like tyrosine kinase inhibitors, due to limited safety data. ^{3 5 6 7 8}

What makes the combination therapy of Anastrozole, Palbociclib, Pertuzumab, and Trastuzumab unique for breast cancer treatment?

This combination therapy is unique because it targets both hormone receptors and the HER2 protein in breast cancer cells, using a mix of drugs that work together to inhibit cancer cell growth and survival. Pertuzumab and Trastuzumab are antibodies that bind to different parts of the HER2 protein, enhancing their effectiveness, while Anastrozole and Palbociclib target hormone receptors and cell cycle processes, respectively, offering a comprehensive approach to treatment. ^{1 2 4 6 9}

Research Team

Amy D. Tiersten

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults with HER2 positive metastatic breast cancer who haven't had systemic treatment for it. They must have certain lab values, be postmenopausal or on ovarian ablation, and agree to use contraception. Excluded are those with severe allergies to similar drugs, uncontrolled medical conditions, recent major surgery or injury, ongoing substance addiction, pregnancy or breastfeeding.

Inclusion Criteria

My brain metastasis has been stable for over 2 weeks after treatment and I'm not on steroids.

My breast cancer is HER2 positive, confirmed by specific tests.

I have not received any systemic treatment for my metastatic breast cancer.

Exclusion Criteria

You have had allergic reactions to similar medications in the past.

I am taking certain medications along with my treatment.

My breast cancer is HER2 negative based on specific tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anastrozole, palbociclib, trastuzumab, and pertuzumab as first-line therapy in metastatic HR-positive, HER2-positive breast cancer

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for progression-free survival and incidence of adverse events

2 years

Treatment Details

Interventions

• Anastrozole
• Palbociclib
• Pertuzumab
• Trastuzumab

Trial Overview The study tests a combination of Anastrozole, Palbociclib (a CDK inhibitor), Trastuzumab and Pertuzumab as first-line therapy in HR-positive, HER2-positive metastatic breast cancer patients. It's designed to assess the safety and effectiveness of this all-biologic regimen while also exploring potential biomarkers that could predict response to treatment.

Participant Groups

Group I: HR-positive, Her2-positive Metastatic Breast Cancer Experimental Treatment 4 Interventions

Women and men with HR-positive, HER2-positive Metastatic Breast Cancer on trial of anastrozole, palbociclib, trastuzumab and pertuzumab

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

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Herbert Irving Comprehensive Cancer Center

Collaborator

Trials

36

Recruited

1,300+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Findings from Research

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]

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]

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]

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 phase III trial involving postmenopausal women with HER2 and hormone receptor co-positive metastatic breast cancer, the combination of trastuzumab and anastrozole significantly improved median progression-free survival compared to anastrozole alone.

The combination therapy also showed higher overall response and clinical benefit rates without any new or unexpected adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab : in HER2 and hormone receptor co-positive metastatic breast cancer. Orman, JS., Perry, CM.[2021]

References

1. France pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pertuzumab in the treatment of HER2+ breast cancer. [2019]

6. China 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. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

The expanding role of pertuzumab in the treatment of HER2-positive breast cancer. [2021]

8. Switzerland 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. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Trastuzumab : in HER2 and hormone receptor co-positive metastatic breast cancer. [2021]