Radiation Therapy + Trastuzumab for Breast Cancer

No longer recruiting at 1443 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anthracyclines

Disqualifiers: Invasive breast cancer, Cardiac disease, Uncontrolled hypertension, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of radiation therapy for treating women with ductal carcinoma in situ (DCIS), a type of early breast cancer, when used alone or with trastuzumab. Trastuzumab, a monoclonal antibody, can help stop tumor growth and spread. Participants are randomly assigned to receive either radiation alone or radiation with trastuzumab. Women who have had a lumpectomy and have HER2-positive DCIS, a specific protein that promotes cancer growth, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have uncontrolled hypertension or certain cardiac conditions, you may not be eligible to participate.

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

Research shows that trastuzumab, often combined with other treatments for HER2-positive breast cancer, is generally well-tolerated. Studies have found that both the original form (Herceptin) and its biosimilars usually have a manageable safety profile. Past studies identified heart-related side effects as the main concern, but these are rare and often mild.

Whole breast irradiation targets and kills cancer cells and is a common, generally safe method. Some patients may experience temporary side effects like skin irritation or tiredness, but these are usually mild and resolve after treatment.

Overall, extensive studies have examined the combination of trastuzumab and whole breast irradiation. While any treatment carries risks, existing evidence suggests these treatments are generally safe and manageable for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of whole breast irradiation (WBI) with trastuzumab for breast cancer because it offers a novel approach to treatment. Unlike standard treatments that focus solely on radiation or chemotherapy, trastuzumab is a targeted therapy specifically designed to latch onto the HER2 protein, which is overexpressed in some breast cancers. This means it can potentially enhance the effectiveness of radiation therapy by specifically targeting and attacking cancer cells with HER2. Additionally, the use of trastuzumab intravenously during specific weeks of the radiation schedule is a new strategy, providing a synergistic effect that could improve outcomes for patients with HER2-positive breast cancer.

What evidence suggests that radiation therapy with trastuzumab could be effective for ductal carcinoma in situ?

This trial will compare the effects of whole breast irradiation (WBI) alone with WBI combined with trastuzumab. Research has shown that combining trastuzumab with whole breast radiation can significantly reduce the risk of breast cancer recurrence. Studies have found a substantial drop in recurrence rates and a notable decrease in breast cancer-related deaths. This combination can nearly halve the risk of cancer returning within three years. Thus, adding trastuzumab to radiation therapy may improve outcomes for women with ductal carcinoma in situ, a type of breast cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Melody A Cobleigh

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for women who've had a lumpectomy to remove ductal carcinoma in situ (DCIS) that's HER2-positive. They should have no DCIS at the surgery margins, be cancer-free elsewhere, and not pregnant or breastfeeding. Participants must be relatively healthy with an ECOG status of 0 or 1 and able to follow up long-term.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form

My breast cancer is classified as DCIS.

Exclusion Criteria

I have had breast cancer or DCIS before.

I have been cancer-free for over 5 years and at low risk of it coming back.

I have suspicious masses or calcifications that have not been biopsied.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks. In Arm II, patients also receive trastuzumab intravenously over 30-90 minutes once in weeks 1 and 4.

5-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 6 months for 5 years and then every 12 months for 5 years.

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab
• Whole Breast Irradiation

Trial Overview The study compares radiation therapy alone versus radiation combined with Trastuzumab, a monoclonal antibody that targets tumor cells. It aims to discover if adding Trastuzumab improves treatment outcomes for HER2-positive DCIS after lumpectomy.

How Is the Trial Designed?

Group I: Arm II (WBI, trastuzumab) Experimental Treatment 3 Interventions

Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I.

Group II: Arm I (standard WBI) Experimental Treatment 2 Interventions

Patients undergo standard WBI over 5-6 weeks.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

In a study of 1,503 patients with early-stage HER-2-positive breast cancer, concurrent treatment with trastuzumab and radiotherapy did not lead to an increase in acute adverse events after surgery, indicating a favorable safety profile.

While there was a higher incidence of leukopenia in patients receiving trastuzumab compared to those who did not, the overall rates of cardiac events remained low and stable, suggesting that the combination treatment is safe in terms of cardiac health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. Halyard, MY., Pisansky, TM., Dueck, AC., 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]

Trastuzumab, when combined with chemotherapy, significantly improves survival rates for patients with early-stage HER2-positive breast cancer, but it can cause cardiotoxicity in a small number of patients.

Caution is advised when irradiating the left breast or thoracic wall in patients receiving trastuzumab, as the long-term effects of combining this therapy with radiotherapy are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. Marinko, T., Dolenc, J., Bilban-Jakopin, C.[2022]

In a study of 55 patients with metastatic HER2-positive breast cancer, the combination of pertuzumab and trastuzumab with locoregional radiotherapy was well tolerated, with only 5.4% experiencing significant skin toxicity and no major gastrointestinal or cardiac side effects.

The treatment showed promising safety, allowing for effective local management of the disease, as indicated by a median follow-up of 4.1 years and a minimal change in heart function after radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab and Trastuzumab Combination with Concomitant Locoregional Radiotherapy for the Treatment of Breast Cancers with HER2 Receptor Overexpression. Aboudaram, A., Loap, P., Loirat, D., et al.[2021]

Trastuzumab significantly improves survival rates in breast cancer patients with HER2 overexpression, but it is associated with an increased risk of cardiac toxicity, particularly in patients who have previously received anthracyclines.

The mechanism of trastuzumab-related cardiac toxicity is not fully understood, but it may sensitize heart cells to stress and injury, leading to myocardial dysfunction without causing visible structural damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. Bria, E., Cuppone, F., Milella, M., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10969053/

Comparative Effectiveness and Safety of Trastuzumab ... The primary safety outcome was death within 30 days of the last dose of neoadjuvant/adjuvant trastuzumab for HER2+ breast cancer. Secondary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8324484/

Trastuzumab for early-stage, HER2-positive breast cancer Pooled analysis of all trials found a highly significant reduction in recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001; figure 1) and breast cancer mortality ...

3. nature.com nature.com/articles/s41523-024-00652-4

The survival benefit of adjuvant trastuzumab with or without ... Cumulatively, they found that the addition of trastuzumab improved OS and reduced the 3-year breast cancer recurrence risk by nearly half.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949713225000977

Healthcare costs and health outcomes analysis of ... No significant difference in DFS (3 years) was found between the neoadjuvant and adjuvant Trastuzumab groups. •. Treatment costs did not differ ...

5. herceptin.com herceptin.com/hcp/adjuvant-breast-cancer/efficacy/clinical-results.html

Herceptin Clinical Trial Results Review information on clinical studies for Herceptin® (trastuzumab) in HER2+ Adjuvant Breast Cancer. See Full Safety and Boxed Warnings for more ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38534957/

Comparative Effectiveness and Safety of Trastuzumab ... Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars.

7. nature.com nature.com/articles/s41598-025-97923-2

Real-world data on trastuzumab emtansine (TDM1) ... This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2203690

Trastuzumab Deruxtecan in Previously Treated HER2-Low ... This trial showed significantly longer progression-free survival and overall survival with trastuzumab deruxtecan than with the physician's ...