Anti-HER2 Therapies for Breast Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Mayo Clinic

Must be taking: Anti-HER2 therapies

Must not be taking: Systemic steroids

Disqualifiers: Immunocompromised, HIV positive, others

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

Compensation: Varies

Number of Visits: 3

Duration: 16 weeks

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how anti-HER2 treatments, such as trastuzumab (Herceptin) and pertuzumab (Perjeta), affect blood cells and tumor tissue in individuals with HER2-positive breast cancer. It aims to understand the interaction between these treatments and cancer cells. The trial includes two groups: one for patients starting new treatments and another for those who have already received therapy. Individuals with HER2-positive breast cancer, either beginning or having completed anti-HER2 therapy, are suitable candidates. Participants will provide blood and tissue samples to help researchers learn more about treatment responses. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you cannot participate if you are on systemic steroid therapy or other immunosuppressive treatments within 30 days before joining. Inhaled steroids and low-dose corticosteroids are allowed.

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

A previous study tested the safety of lapatinib in over 12,000 people with HER2-positive breast cancer. Common side effects included diarrhea, rash, and nausea. Most participants tolerated it well, but some experienced more serious issues like heart problems.

Research has shown that neratinib treats HER2-positive breast cancer and has been studied in large groups. It is effective but can cause diarrhea, which is often controlled with medication.

Studies have found that pertuzumab is generally safe, but about 11% of participants may experience allergic reactions. Some also had heart issues, especially when combined with certain chemotherapy drugs.

Lastly, trastuzumab has been widely used and studied for HER2-positive breast cancer. It can lower the chance of cancer recurrence but may cause heart problems and other side effects like fever or chills.

Overall, these treatments are well-researched and generally tolerated by patients, though each has specific side effects to consider. Always consult a doctor about the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the focus on anti-HER2 therapies like Lapatinib, Neratinib, Pertuzumab, and Trastuzumab for HER2-positive breast cancer because these treatments specifically target the HER2 protein, which promotes the growth of cancer cells. Unlike some traditional chemotherapy treatments that affect both healthy and cancerous cells, these therapies are designed to inhibit HER2 activity directly, potentially leading to more effective and less toxic treatment options. Additionally, exploring immune response to these therapies could uncover new insights into how to improve treatment outcomes and manage resistance, paving the way for personalized cancer care.

What evidence suggests that this trial's treatments could be effective for HER2 positive breast cancer?

Research has shown that treatments targeting HER2 effectively treat HER2-positive breast cancer. In this trial, participants may have previously received or completed anti-HER2 therapies, including trastuzumab, pertuzumab, lapatinib, and neratinib. Studies on trastuzumab have demonstrated that it significantly lowers the chances of cancer recurrence and reduces death rates in early-stage cases, with patients experiencing about a 34% lower risk of cancer returning. Pertuzumab has slowed disease progression, with long-term data indicating better survival rates. Lapatinib, when combined with other treatments, has helped patients live longer without disease worsening, showing its potential to control the disease. Neratinib has extended the time patients remain disease-free, especially after trastuzumab treatment. Overall, strong evidence supports the use of these treatments for HER2-positive breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Saranya Chumsri, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Inclusion Criteria

Histological confirmed adenocarcinoma of the breast stage I-IV from the American Joint Committee on Cancer staging 8th edition

Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR gene amplification on fluorescence in situ hybridization (FISH) ratio >= 2.0

Scheduled to start new anti-HER2 therapy/therapies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-HER2 therapies such as trastuzumab, pertuzumab, lapatinib, or neratinib. Blood samples are collected at baseline, 8 and 16 weeks after starting treatment.

16 weeks

3 visits (in-person) for blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment, with additional blood sample collection at the time of disease recurrence or progression.

Up to 2 years or until disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Biospecimen Collection
• Lapatinib
• Neratinib
• Pertuzumab
• Trastuzumab

How Is the Trial Designed?

Group I: Observational Tissue-Only Cohort Experimental Treatment 1 Intervention

For patients with stage I-IV disease who received or previously completed anti-HER2 therapy, tissue samples from previous biopsy and/or surgical resection are collected on study.

Group II: Observational Blood & Tissue Cohort Experimental Treatment 1 Intervention

Patients with stage I-III disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. Patients with stage IV disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of progressive disease. Patients with stage IV disease with no disease progression ≥ 2 years on the same line of therapy undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. For all patients, tissue samples from previous biopsy and/or surgical resection are also collected on study.

Lapatinib is already approved in United States, European Union for the following indications:

Approved in United States as Tykerb for:

• Advanced or metastatic breast cancer in combination with capecitabine for patients whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab

Approved in European Union as Tyverb for:

• Advanced or metastatic breast cancer in combination with capecitabine for patients whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8351035/

The Effectiveness of Lapatinib in HER2-Positive Metastatic ... Our results suggest that treatment regimen containing lapatinib may be a therapeutic alternative for heavily treated HER2 positive breast cancer ...

2. ecancer.org ecancer.org/en/journal/article/1758-her2-positive-metastatic-breast-cancer-treated-with-low-dose-lapatinib-in-a-resource-constrained-setting-in-south-india-a-retrospective-audit

Her2 positive metastatic breast cancer treated with low ... The disease control rate with lapatinib was 61.7%. The median progression-free survival was 7 months (95% CI: 5.6–8.4 months). The median ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41587-1/fulltext

A phase II study of lapatinib monotherapy in chemotherapy ... Both assessments established that ∼6% of HER2-positive patients derived clinical benefit from lapatinib, being progression free for ≥6 months. No objective ...

4. systematicreviewsjournal.biomedcentral.com systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-022-02134-9

Lapatinib and lapatinib plus trastuzumab therapy versus ... The CHER-Lob and TRIO-US B07 proved that trastuzumab plus lapatinib treatment has a better pathologic complete response (pCR) outcome [21, 22].

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa064320

Lapatinib plus Capecitabine for HER2-Positive Advanced ... The median time to progression was 8.4 months in the combination-therapy group and 4.4 months in the monotherapy group. On the basis of the ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/022059s023lbl.pdf

TYKERB® (lapatinib) tablets, for oral use - accessdata.fda.gov HER2-Positive Metastatic Breast Cancer: The safety of TYKERB has been evaluated in more than 12,000 ... For people with hormone receptor-positive, HER2-positive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3336826/

Lapatinib for Advanced or Metastatic Breast Cancer - PMC It is registered for the treatment of advanced or metastatic HER-2 + breast cancer in combination with capecitabine and for hormone receptor–positive breast ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02342587

NCT02342587 | Safety and Clinical Activity of Lapatinib in ... Data suggest that a dual ErbB1 and ErbB2 inhibitor may provide improved therapeutic benefit compared with inhibitors that target only one or the other receptor.

9. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1729

Preliminary safety data of preoperative chemotherapy plus ... Preliminary safety data of preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2-positive operable breast cancer ; Results.

10. gsk.com gsk.com/en-gb/media/press-releases/data-from-tykerb-investigational-phase-iii-studies-in-neo-adjuvant-her2-positive-breast-cancer-presented-at-breast-cancer-symposium/

Data from Tykerb investigational phase III studies in neo- ... Topline results were presented today from two Phase III studies examining the effect of Tykerb (lapatinib) in the neo-adjuvant setting of HER2- ...