Combination Therapy for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of four medicines for treating a specific type of metastatic breast cancer with hormone receptor-positive and HER2-positive markers. Researchers aim to determine the safety and effectiveness of using these medicines together. They also seek indicators that might predict the treatment's success or failure. Suitable participants have not yet received treatment for their metastatic breast cancer and have been diagnosed with hormone receptor-positive, HER2-positive breast cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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.

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

Research has shown that using anastrozole, palbociclib, trastuzumab, and pertuzumab together is generally safe. One study found that 97% of patients experienced positive results with these drugs, indicating most benefited without serious side effects.

The study also identified the safest dose for these medications, ensuring safe administration to patients.

These drugs are typically used separately to treat breast cancer. While using them together is new, they are known to be safe when used alone or in other combinations, providing confidence about their safety in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for HR-positive, HER2-positive metastatic breast cancer because it uniquely combines anastrozole, palbociclib, pertuzumab, and trastuzumab to target cancer cells in multiple ways. While standard treatments often focus on either hormone receptor or HER2 pathways, this combination tackles both simultaneously. Anastrozole decreases estrogen production, palbociclib inhibits cancer cell division, and pertuzumab and trastuzumab target HER2 receptors. This multi-pronged approach could potentially enhance effectiveness and delay resistance compared to current therapies that typically target only one pathway.

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

Research has shown that a combination of four drugs—anastrozole, palbociclib, trastuzumab, and pertuzumab—holds promise for treating HR-positive, HER2-positive metastatic breast cancer. In one study, 97% of patients benefited from this combination, indicating it helped most of them. Specifically, adding pertuzumab to trastuzumab and anastrozole (a hormone therapy) improved the duration patients lived without their cancer worsening. Palbociclib, when used with these treatments, also slowed cancer progression. These findings suggest this combination could be effective for individuals with this type of breast cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Amy D. Tiersten

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03304080

Anastrozole, Palbociclib, Trastuzumab and Pertuzumab in ... 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 ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/RF02-01/744290/Abstract-RF02-01-A-Multicenter-Phase-I-II-Trial-of

Abstract RF02-01: A Multicenter, Phase I/II Trial of Anastrozole ... The combination of anastrozole, palbociclib, trastuzumab, and pertuzumab was well tolerated and effective with a clinical benefit rate of 97% in pts with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.TPS1103

A multicenter, phase I/II trial of anastrozole, palbociclib ... Studies suggest that this 10% of all breast cancer cases may derive less benefit from endocrine therapy than those with HR+ disease without HER2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10102835/

Pertuzumab, Trastuzumab, and an Aromatase Inhibitor for ... Adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS)

5. targetedonc.com targetedonc.com/view/palbociclib-combo-shows-benefit-to-pfs-in-hr-her2-breast-cancer

Palbociclib Combo Shows Benefit to PFS in HR+, HER2+ ... Progression-free survival was superior with first-line maintenance of palbociclib in HR-positive, HER2-positive metastatic breast cancer.

6. mountsinai.org mountsinai.org/clinical-trials/anastrozole-palbociclib-trastuzumab-pertuzumab-in-her-positive-her2-positive-metastatic-breast

Anastrozole, Palbociclib, Trastuzumab and Pertuzumab in ... 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 ...