Intraoperative Radiation Therapy for Breast Cancer

Recruiting at 24 trial locations

Overseen By Michael Alvarado

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Chemotherapy, Hormone therapy

Disqualifiers: Lymph node positive, BRCA1/2, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 15-40 minutes

1259 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are undergoing primary systemic treatment (hormones or chemotherapy) as initial treatment, you are not eligible for the trial.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are undergoing primary systemic treatment like hormones or chemotherapy, you may not be eligible for the trial.

What data supports the idea that Intraoperative Radiation Therapy for Breast Cancer is an effective treatment?

The available research shows that combining radiation therapy with pembrolizumab, a drug also known as Keytruda, can improve outcomes in breast cancer treatment. Specifically, a study investigated this combination in patients with hormone receptor-positive metastatic breast cancer and found it to be beneficial. Additionally, there is interest in combining radiation with immunotherapy to enhance immune responses against cancer, which has shown promise in early clinical trials. This suggests that Intraoperative Radiation Therapy, when combined with pembrolizumab, could be an effective treatment for breast cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Intraoperative Radiation Therapy, Keytruda, pembrolizumab for breast cancer?

Research shows that combining radiation therapy with pembrolizumab (Keytruda) can enhance immune responses against cancer. This combination has shown promise in improving outcomes in breast cancer and other solid tumors by altering the tumor environment and boosting the body's immune attack on cancer cells. ^{1 2 3 4 5}

What safety data exists for Intraoperative Radiation Therapy for Breast Cancer?

The provided research does not contain specific safety data for Intraoperative Radiation Therapy for Breast Cancer. However, it includes safety data for pembrolizumab (Keytruda), an immune checkpoint inhibitor. Pembrolizumab is associated with immune-related adverse events such as pneumonitis (1%-5% of patients), type 1 diabetes mellitus (0.2% of cases), and other immune-mediated reactions like colitis, hepatitis, and thyroid disorders. These findings are relevant if pembrolizumab is part of the treatment protocol. ^{2 4 6 7 8}

Is pembrolizumab (Keytruda) safe for humans?

Pembrolizumab (Keytruda) is generally considered safe for humans, but it can cause some side effects. These include fatigue, cough, nausea, and more serious immune-related issues like pneumonitis (lung inflammation) and type 1 diabetes in rare cases. ^{2 4 6 7 8}

Is the drug Intraoperative Radiation Therapy (also known as Keytruda, pembrolizumab) a promising treatment for breast cancer?

Keytruda (pembrolizumab) is a drug that has shown promise in treating various cancers, including lung cancer and melanoma, by helping the immune system fight cancer cells. It has been approved for use in several types of cancer, suggesting it could be a promising option for breast cancer as well. ^{1 2 4 8 9}

How does the drug pembrolizumab (Keytruda) differ from other treatments for breast cancer?

Pembrolizumab (Keytruda) is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly kills cancer cells. ^{1 2 4 8 9}

What is the purpose of this trial?

This phase IV trial studies the side effects of intraoperative radiation therapy and how well it works in treating patients with breast cancer undergoing breast-conserving surgery. Delivering radiation one time to the area where the tumor was removed while the patient is still in the operating room may kill any residual tumor cells and may be as effective as standard radiation therapy in patients with early stage breast cancer.

Research Team

Michael D. Alvarado

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for individuals with early stage breast cancer (T1 and T2, no larger than 3.5 cm, no spread to lymph nodes or other parts of the body) who are suitable for breast-conserving surgery. It's not open to those under 50, with tumors over 3 cm, estrogen receptor negative cancers, HER2 positive status, high-grade tumors or extensive intraductal component.

Inclusion Criteria

I am a candidate for surgery that will not remove my entire breast.

My cancer is small (under 3.5 cm) and has not spread to lymph nodes or other parts of my body.

Exclusion Criteria

Unable to determine if the edges of the tissue removed during surgery are clear of cancer.

I was diagnosed with cancer in both breasts at the same time.

My breast cancer has spread to the lymph nodes under my arm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intraoperative radiation therapy (IORT) in a single fraction over 15-40 minutes during breast-conserving surgery

15-40 minutes

1 visit (in-person, during surgery)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 6 months for 3 years and yearly for 2 additional years

5 years

Every 6 months for 3 years, then yearly for 2 years

Treatment Details

Interventions

• Intraoperative Radiation Therapy

Trial Overview The study is testing intraoperative radiation therapy given one time during surgery where the tumor was removed. The goal is to see if this method can effectively kill any remaining tumor cells and compare its effectiveness against standard radiation treatments in patients with early-stage breast cancer.

Participant Groups

Group I: Treatment (IORT) Experimental Treatment 2 Interventions

Patients undergo IORT in a single fraction over 15-40 minutes at the time of standard of care lumpectomy.

Intraoperative Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Keytruda for:

• Head and neck squamous cell carcinoma (HNSCC)
• Melanoma
• Lung cancer

Approved in European Union as Keytruda for:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Head and neck squamous cell carcinoma (HNSCC)

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Carl Zeiss Meditec AG

Industry Sponsor

Trials

43

Recruited

7,800+

Findings from Research

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Radiation therapy not only helps eliminate cancer cells but also modifies the tumor microenvironment, potentially enhancing the body's immune response against tumors.

Combining radiation with immune checkpoint inhibitors has shown promise in early clinical trials for breast cancer, suggesting a synergistic effect that could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Combining Radiation and Immunotherapy in Breast Cancer. Nguyen, AT., Shiao, SL., McArthur, HL.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study involving 8 patients with hormone receptor-positive metastatic breast cancer, combining pembrolizumab with palliative radiation therapy did not result in any objective responses, leading to the study's closure.

The median progression-free survival was only 1.4 months and overall survival was 2.9 months, indicating limited efficacy of this treatment combination in heavily pre-treated patients, although the treatment was generally safe with only one significant adverse event reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Barroso-Sousa, R., Krop, IE., Trippa, L., et al.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Advances in Combining Radiation and Immunotherapy in Breast Cancer. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

New Approved Use for Keytruda. [2022]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]