Radiation Therapy + Olaparib for Breast Cancer

Recruiting at 262 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Uncontrolled infection, Heart failure, others

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

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

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking strong or moderate CYP3A inhibitors at least 2 weeks before starting olaparib and strong or moderate CYP3A inducers at least 5 weeks before. You also cannot take any additional anti-cancer therapy during the trial.

What data supports the effectiveness of the treatment Radiation Therapy + Olaparib for Breast Cancer?

Research shows that radiotherapy, including intraoperative radiotherapy (IORT), is effective in controlling local and regional breast cancer and improving quality of life by relieving pain from metastases. Additionally, IORT has been associated with favorable outcomes in early-stage breast cancer, suggesting its potential effectiveness when combined with other treatments like Olaparib. ^{1 2 3 4 5}

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

Radiation therapy, including advanced techniques like image-guided radiotherapy (IGRT), is generally considered safe and is commonly used in clinical practice, though it can have some side effects. However, there is limited long-term safety data on using new targeted agents like olaparib concurrently with radiation therapy for breast cancer. ^{6 7 8 9 10}

How is the treatment of Radiation Therapy + Olaparib unique for breast cancer?

This treatment combines radiation therapy, which targets and kills cancer cells in the breast, with Olaparib, a drug that blocks an enzyme (PARP) involved in repairing damaged DNA in cancer cells, making it harder for them to survive. This combination is unique because it uses both a targeted drug and radiation to potentially enhance the effectiveness of treatment for breast cancer. ^{1 3 6 11 12}

What is the purpose of this trial?

This phase II trial studies how well radiation therapy with or without olaparib works in treating patients with inflammatory breast cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. It is not yet known whether radiation therapy with or without olaparib may work better in treating patients with inflammatory breast cancer.

Research Team

Reshma Jagsi

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with inflammatory breast cancer without distant metastases who have completed neoadjuvant chemotherapy and mastectomy. They must not have had prior radiation to the chest or certain drug treatments during the study, agree to contraception if of childbearing potential, and cannot be breastfeeding. Participants need proper organ function, no uncontrolled diseases or recent major surgeries, and can't be on strong CYP3A inhibitors/inducers.

Inclusion Criteria

I will not get live vaccines while on olaparib and for 30 days after.

I am not planning to receive any other cancer treatments while on the study.

Your alkaline phosphatase levels should be within a certain range, not too high.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive olaparib and/or radiation therapy 5 days per week for 6 weeks

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

Every 3 months until 3 years, then every 6 months

Treatment Details

Interventions

• Olaparib
• Radiation Therapy

Trial Overview The trial is testing whether adding Olaparib (a PARP inhibitor that prevents cancer cells from repairing DNA damage) to standard radiation therapy improves outcomes in patients with inflammatory breast cancer compared to radiation alone. Patients are randomly assigned to one of these two treatment options.

Participant Groups

Group I: Group I (olaparib, radiation therapy) Experimental Treatment 4 Interventions

Patients receive olaparib PO BID the day before standard RT commences (Day 0) and throughout the RT course until the last day of RT administration. Olaparib is also continued on weekends (routine days without RT) throughout the RT course. Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

Group II: Group II (radiation therapy) Active Control 3 Interventions

Patients undergo standard radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

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

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

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 82 patients with early-stage breast cancer treated with intraoperative radiotherapy (IORT), 72% of those who underwent 21-gene recurrence testing were classified as low risk, indicating that IORT may be suitable for a majority of these patients.

The study highlights a need for further research on the long-term clinical outcomes and safety of IORT, as most patients selected for this treatment were low risk based on their recurrence scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

21-gene recurrence assay in patients receiving intraoperative radiotherapy: are "favorable" characteristics a surrogate for low recurrence? Oppong, BA., Sen Gupta, S., Gary, M., et al.[2022]

Intraoperative radiotherapy (IORT) was used in a study involving 1367 patients with 1400 tumors, showing a 5-year local recurrence rate of 5.98% for those receiving IORT only, which is comparable to other IORT studies but higher than standard whole breast radiation therapy (WBRT).

IORT offers benefits such as convenience and low complication rates, making it a viable option for patients meeting specific criteria, although the addition of WBRT was found to significantly reduce the risk of local recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). Silverstein, MJ., Epstein, MS., Chen, P., et al.[2022]

Intraoperative radiotherapy (IORT) for early-stage breast cancer significantly improves radiation-related quality of life (QoL) parameters, with patients reporting less pain and better functioning compared to those receiving external beam radiotherapy (EBRT).

In a study of 230 women, those treated with IORT alone experienced fewer breast and arm symptoms and better overall role functioning, indicating that IORT may be a more patient-friendly option than traditional EBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. Welzel, G., Boch, A., Sperk, E., 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]

In a study of 836 prostate cancer patients, those who received image-guided radiotherapy (IGRT) had a 5-year overall survival rate of 88%, which was not significantly different from the 86% survival rate of patients who did not receive IGRT, indicating that IGRT does not negatively impact survival outcomes.

The study found no significant differences in mortality rates from prostate cancer, other cancers, or cardiovascular issues between the IGRT and non-IGRT groups, suggesting that IGRT is a safe option for localized prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of image-guided radiotherapy in definitive radiotherapy for localized prostate cancer: a population-based analysis. Kuo, YH., Liang, JA., Chen, GH., et al.[2022]

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]

Radiation therapy is crucial in breast cancer treatment, significantly reducing local recurrence and improving survival rates, especially with advancements in techniques since the late 1980s.

Shorter courses of radiation therapy (3-4 weeks) are generally as effective as longer ones, and modern techniques like volumetric modulated arc therapy (VMAT) help minimize complications while enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. Boyages, J., Baker, L.[2020]

References

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[Radiotherapy aspects in the treatment of breast cancer]. [2006]

2. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

21-gene recurrence assay in patients receiving intraoperative radiotherapy: are "favorable" characteristics a surrogate for low recurrence? [2022]

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

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Progress in the surgical management of breast cancer: Present and future. [2015]

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Concurrent Radiation and Modern Systemic Therapies for Breast Cancer: An Ever-Expanding Frontier. [2021]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Safety of image-guided radiotherapy in definitive radiotherapy for localized prostate cancer: a population-based analysis. [2022]

9. Poland pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Randomised Phase II Feasibility Trial of Image-guided External Beam Radiotherapy With or Without High Dose Rate Brachytherapy Boost in Men with Intermediate-risk Prostate Cancer (CCTG PR15/ NCT01982786). [2019]

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

Breast cancer. [2019]

12. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Evolution of radiotherapy techniques in breast conservation treatment. [2020]