Berzosertib + Radiation for Triple-Negative Breast Cancer

Recruiting at 14 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 5-6 weeks

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the best dose of berzosertib combined with radiation therapy for treating certain types of breast cancer. Berzosertib helps stop cancer cell growth by blocking important enzymes, while radiation kills the cancer cells. This combination may work better than radiation alone.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you should avoid medications that strongly affect the enzyme CYP3A4, like certain antibiotics and herbal supplements, for 14 days before starting the trial. It's important to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of the treatment Berzosertib + Radiation for Triple-Negative Breast Cancer?

Research shows that post-operative radiotherapy can improve survival and reduce recurrence in triple-negative breast cancer patients with four or more positive lymph nodes. This suggests that radiation therapy, as part of the treatment, may be beneficial for certain patients with this type of cancer. ^{1 2 3 4 5}

Is the combination of Berzosertib and radiation therapy generally safe for humans?

The safety of radiation therapy techniques like Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiotherapy (IGRT) has been studied, showing improvements in sparing normal tissues and reducing adverse events in some cancer treatments. However, specific safety data for Berzosertib combined with radiation therapy is not provided in the available research. ^{6 7 8 9 10}

What makes the treatment of Berzosertib + Radiation unique for triple-negative breast cancer?

The combination of Berzosertib, a drug that targets DNA repair, with radiation therapy is unique because it aims to enhance the effectiveness of radiation by preventing cancer cells from repairing the damage caused by the radiation, potentially overcoming resistance seen with traditional chemotherapy in triple-negative breast cancer. ^{11 12 13 14 15}

Research Team

Robert W Mutter

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

Adults over 18 with certain types of breast cancer (triple-negative or hormone receptor-positive, HER2-negative) that didn't respond to chemotherapy can join. They must have completed surgery and possibly postoperative chemo recently, be in good health otherwise, and agree to use contraception. People with recent chemo, prior radiation in the same area, uncontrolled illnesses, or known hypersensitivity to similar drugs are excluded.

Inclusion Criteria

I had immediate reconstruction after my mastectomy.

My breast cancer is triple-negative or has low hormone receptor levels, and I've had specific chemotherapy.

I am not pregnant or able to become pregnant, and will use birth control during and after the study.

Exclusion Criteria

I have recovered from previous cancer treatment side effects, except for hair loss and mild nerve pain.

I have not had chemotherapy in the last 4 weeks.

You had allergic reactions to drugs similar to berzosertib.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive berzosertib intravenously twice weekly and undergo radiation therapy 5 days a week for 5-6 weeks

5-6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Weekly visits (in-person)

Long-term Follow-up

Participants are followed up at 12 months, then yearly for up to 3 years to assess long-term outcomes

Up to 3 years

Treatment Details

Interventions

• Berzosertib
• Radiation Therapy

Trial Overview The trial is testing Berzosertib combined with standard radiation therapy against breast cancer that resisted chemotherapy. It aims to find the best dose of Berzosertib which blocks enzymes needed for cell growth and may enhance the effectiveness of radiation therapy.

Participant Groups

Group I: Treatment (berzosertib, radiation therapy) Experimental Treatment 5 Interventions

Patients receive berzosertib IV over 60 minutes BIW for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo RT 5 days a week for 5-6 weeks depending on the type of surgery undergone. Patients also undergo a collection of blood on study.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 658 patients with high-risk endometrial cancer, intensity-modulated radiation therapy (IMRT) was associated with significantly fewer grade ≥2 adverse events, such as diarrhea and hematologic issues, compared to 3-dimensional conformal radiation therapy (3DCRT) during follow-up.

IMRT also showed a trend towards fewer patient-reported symptoms like bowel urgency and abdominal cramps during treatment, indicating it may provide a better quality of life for patients undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy. Wortman, BG., Post, CCB., Powell, ME., et al.[2022]

Prostate cancer patients receiving image-guided radiotherapy (IGRT) experienced significantly less severe acute toxicity, such as urinary frequency, diarrhoea, and fatigue, compared to those who did not receive IGRT, with 23% vs 7% for urinary frequency ≥G3 and 15% vs 3% for diarrhoea ≥G2.

The onset of these toxicities was earlier in the non-IGRT group, indicating that IGRT not only reduces the severity of symptoms but also delays their onset, leading to a more tolerable treatment experience for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Gill, S., Thomas, J., Fox, C., et al.[2021]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

Image-guided Radiotherapy (IGRT) enhances the effectiveness of Intensity-Modulated Radiotherapy (IMRT) by addressing the challenges of organ and target motion in pelvic treatments, which is crucial for safely delivering higher doses to cervical cancer patients.

Implementing IGRT solutions is essential to minimize the risk of geographic miss targeting and overdose to organs at risk, thereby improving treatment outcomes and reducing toxicity in cervical cancer radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Problems and solutions in IGRT for cervical cancer. Ríos, I., Vásquez, I., Cuervo, E., et al.[2020]

In a study using various mouse models of triple negative breast cancer (TNBC), the combination of nintedanib (an antiangiogenic drug) and paclitaxel (PTX) showed enhanced antitumor efficacy in both primary and metastatic settings, indicating a potential new treatment strategy for TNBC.

The triple combination of nintedanib, PTX, and a PD-L1 antibody demonstrated optimal efficacy in advanced metastatic models, suggesting that this combination could improve treatment outcomes for patients with TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer. Reguera-Nuñez, E., Xu, P., Chow, A., et al.[2023]

References

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

Post-operative radiotherapy is beneficial for T1/T2 triple negative breast cancer patients with four or more positive lymph nodes. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Intraoperative Radiotherapy Tumour Bed Boost during Breast-Conserving Surgery after Neoadjuvant Chemotherapy - a Subgroup Analysis of Hormone Receptor-Positive HER2-Negative Breast Cancer. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Survival and local control rates of triple-negative breast cancer patients treated with boost-IOERT during breast-conserving surgery. [2022]

4. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Tumor bed boost radiotherapy in breast cancer. A review of current techniques. [2012]

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

Post-mastectomy Radiation Therapy in Triple-Negative Breast Cancer Patients: Analysis of the BEATRICE Trial. [2022]

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

Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy. [2022]

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

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. [2021]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

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

Electronic brachytherapy for postsurgical adjuvant vaginal cuff irradiation therapy in endometrial and cervical cancer: a retrospective study. [2016]

10. Poland pubmed.ncbi.nlm.nih.gov

Problems and solutions in IGRT for cervical cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Triple-negative breast cancer drug resistance, durable efficacy, and cure: how advanced biological insights and emerging drug modalities could transform progress. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Regorafenib sensitizes human breast cancer cells to radiation by inhibiting multiple kinases and inducing DNA damage. [2022]

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

Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation. [2021]

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

Targeted Treatment of Triple-Negative Breast Cancer. [2021]

15. England pubmed.ncbi.nlm.nih.gov

Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer. [2023]