Radiation Therapy + Trastuzumab for Breast Cancer

Recruiting at 1411 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

2014 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase III trial studies radiation therapy to see how well it works with or without trastuzumab in treating women with ductal carcinoma in situ who have undergone lumpectomy. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy is more effective with or without trastuzumab in treating ductal carcinoma in situ.

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 the combination of radiation therapy and trastuzumab safe for humans?

Research suggests that combining radiation therapy with trastuzumab is generally safe, with no significant increase in harmful side effects. However, caution is advised when combining radiation with certain other drugs, as the safety data is limited. ^{1 2 3 4 5}

What makes the treatment of Radiation Therapy + Trastuzumab for Breast Cancer unique?

This treatment is unique because it combines whole breast irradiation (a type of radiation therapy targeting the entire breast) with trastuzumab, a drug that specifically targets HER2-positive breast cancer cells, potentially enhancing the effectiveness of radiation by making cancer cells more sensitive to it. This combination is particularly novel as it is used concurrently, which is not the standard approach for all breast cancer treatments. ^{5 6 7 8 9}

What data supports the effectiveness of the drug Trastuzumab for breast cancer?

Research shows that Trastuzumab significantly improves survival rates in breast cancer patients with HER2-positive tumors, both in early and advanced stages. It is often used with other treatments like chemotherapy and radiotherapy to enhance its effectiveness. ^{1 7 8 10 11}

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

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 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]

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]

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 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]

Citations

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

Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. [2022]

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

Preliminary results of whole brain radiotherapy with concurrent trastuzumab for treatment of brain metastases in breast cancer patients. [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer. [2022]

4. United States 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. [2019]

6. France pubmed.ncbi.nlm.nih.gov

Combination of radiotherapy and double blockade HER2 with pertuzumab and trastuzumab for HER2-positive metastatic or locally recurrent unresectable and/or metastatic breast cancer: Assessment of early toxicity. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study. [2020]

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. France pubmed.ncbi.nlm.nih.gov

[Concurrent radiation therapy and dual HER2 blockade in breast cancer: Assessment of toxicity]. [2021]

10. France pubmed.ncbi.nlm.nih.gov

[Concurrent whole-brain radiotherapy with trastuzumab for treatment of brain metastases in breast cancer patients: questions and answers]. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Pertuzumab and Trastuzumab Combination with Concomitant Locoregional Radiotherapy for the Treatment of Breast Cancers with HER2 Receptor Overexpression. [2021]