Radiation Therapy + Olaparib for Breast Cancer

Not currently recruiting at 270 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the effectiveness of combining radiation therapy with the drug olaparib for treating inflammatory breast cancer. Radiation therapy uses high-energy x-rays to target and kill tumor cells, while olaparib, a targeted therapy, blocks the enzyme PARP to prevent cancer cells from repairing damaged DNA. The study compares the effects of radiation therapy alone to radiation therapy combined with olaparib. Individuals who have completed chemotherapy and a mastectomy for inflammatory breast cancer, without distant spread, may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that olaparib, a drug tested in this trial, has promising safety results from earlier studies. One study found that fewer people died when taking olaparib compared to a placebo (a pill with no active drug). Specifically, 59 deaths occurred in the olaparib group and 86 in the placebo group, suggesting olaparib might be safer than not taking any treatment. Other studies have also found that patients using olaparib lived longer.

Olaparib is already approved for treating certain breast cancers with BRCA mutations, indicating it has passed strict safety tests for those uses. However, like all treatments, it can have side effects. Common side effects of olaparib include nausea, tiredness, and low blood cell counts, but these are usually manageable.

In summary, olaparib has been well-studied and is generally considered safe for its approved uses, though side effects can occur. Always consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for breast cancer, which often involve surgery, chemotherapy, or hormone therapy, this investigational approach combines olaparib with radiation therapy. Olaparib is a PARP inhibitor, which means it targets cancer cells by preventing them from repairing their DNA, potentially enhancing the effects of radiation. Researchers are excited about this combination because it could offer a more targeted attack on cancer cells, possibly improving treatment outcomes while minimizing damage to healthy tissue. This approach may lead to fewer side effects compared to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for inflammatory breast cancer?

This trial will compare the effects of combining olaparib with radiation therapy versus using radiation therapy alone for treating breast cancer. Research has shown that olaparib, when combined with radiation therapy, could be promising for treating breast cancer. Studies have found that olaparib works well for patients with certain genetic changes, like BRCA mutations, often leading to better survival rates. For instance, one study found that 87.5% of patients treated with olaparib were alive after six years, compared to 83.2% in a comparison group. Olaparib blocks a protein called PARP, which helps repair damaged DNA in cancer cells. This blockage can cause cancer cells to die because they can't repair themselves. While olaparib is particularly effective for some types of breast cancer, using it with radiation might enhance its effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

Reshma Jagsi

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39544591/

Real-World Clinical Outcomes of Treatment With Olaparib ... Olaparib is effective in the treatment of metastatic breast cancer (MBC) patients, mainly confirmed by deleterious germline BRCA mutations.

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

LYNPARZA® (olaparib) demonstrated clinically meaningful ... 87.5% of patients treated with LYNPARZA were alive at six years vs. 83.2% in the comparator arm. First and only PARP inhibitor to improve ...

3. lynparza.com lynparza.com/breast-cancer/results/early-breast-cancer.html

Early Breast Cancer - Clinical Study Results of ... LYNPARZA lowered the risk of death by 32% in early breast cancer compared with placebo. In this study, 846 out of 921 patients treated with LYNPARZA were alive ...

4. lynparzahcp.com lynparzahcp.com/breast-cancer/efficacy/olympiad.html

LYNPARZA® (olaparib) Efficacy for gBRCAm, HER2-negative ... LYNPARZA significantly improved PFS vs physician's choice of chemotherapy in the OlympiAD trial. 1,2 Primary endpoint: progression-free survival.

5. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

Lynparza demonstrated clinically meaningful prolonged ... 87.5% of patients treated with Lynparza were alive at six years vs. 83.2% in the comparator arm. First and only PARP inhibitor to improve ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10948524/

Clinical effectiveness and safety of olaparib in BRCA-mutated ... The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated ...

7. dana-farber.org dana-farber.org/newsroom/news-releases/2024/parp-inhibition-shows-long-term-survival-benefits-for-patients-with-high-risk-brca-positive-breast-cancer

PARP Inhibition Shows Long-term Survival Benefits for ... After a median follow-up of 6.1 years, patients treated with olaparib continued to show significant improvements in survival outcomes, in both ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2105215

Adjuvant Olaparib for Patients with BRCA1- or BRCA2- ... Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, ...

9. lynparzahcp.com lynparzahcp.com/breast-cancer/safety-tolerability/olympiad.html

gBRCAm, HER2-Negative, Metastatic Breast Cancer Learn about the safety and tolerability for LYNPARZA® (olaparib) in the OlympiAD trial for patients with gBRCAm, HER2-negative, metastatic breast cancer.