Rucaparib + Radiation for Breast Cancer

No longer recruiting at 8 trial locations

Overseen By Simon Powell, MD, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: PARP inhibitors

Disqualifiers: Pregnancy, Breast implants, Prior radiation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer drug, Rucaparib, combined with radiation therapy, to determine its safety for treating certain types of breast cancer. The focus is on women with specific forms of breast cancer that haven't spread beyond the breast. It may suit women who have undergone surgery but still have cancer in the breast or lymph nodes, especially after chemotherapy. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking any cytotoxic chemotherapeutic agents and biologic therapy at least 2 weeks before starting radiation therapy. However, bisphosphonates and maintenance pembrolizumab are allowed during the trial.

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

Studies have shown that Rucaparib, used alone or with other treatments, is generally safe and well-tolerated in patients with certain types of tumors. For instance, a small study combining Rucaparib with another drug found the treatment to be acceptably safe. However, like other PARP inhibitors, it carries a risk of side effects, ranging from mild to severe.

The radiation therapy in this trial is a common treatment for breast cancer patients. Research has shown it effectively reduces the chance of cancer returning after surgery. Some patients may experience side effects like skin irritation and tiredness, but these are usually manageable and temporary.

Both Rucaparib and radiation therapy have proven safety records from their use in other contexts. This trial phase aims to ensure they remain safe when used together. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Unlike the standard treatments for breast cancer, which often include surgery, chemotherapy, and conventional radiation, the combination of Rucaparib with radiation therapy offers a novel approach. Rucaparib is a PARP inhibitor, which means it helps prevent cancer cells from repairing their DNA, making them more susceptible to radiation damage. This unique mechanism enhances the effectiveness of radiation therapy, potentially leading to better outcomes. Researchers are excited because this combination could improve the precision and effectiveness of breast cancer treatment, offering hope for enhanced control of the disease.

What evidence suggests that Rucaparib combined with radiation therapy might be an effective treatment for breast cancer?

In this trial, participants will receive a combination of rucaparib and radiotherapy. Research has shown that rucaparib may help treat certain types of breast cancer, particularly in patients with BRCA1/2 gene mutations. One study found that rucaparib was effective for patients with high levels of genetic instability or non-inherited BRCA mutations. Another study demonstrated that rucaparib, when combined with another drug, was safe and effective in treating tumors with BRCA mutations. Radiotherapy is a well-known treatment that reduces the risk of breast cancer recurrence after surgery. Studies indicate that adding radiation can significantly lower the chance of cancer returning. This trial will explore whether combining rucaparib with radiotherapy might improve treatment outcomes for breast cancer patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Atif Khan, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with triple negative breast cancer (TNBC) or hormone-receptor positive, Her2/neu negative breast cancer who still have signs of the disease after chemotherapy. They must be able to take oral meds, have a life expectancy of at least 6 months, and good organ function. Women who can get pregnant must use birth control or abstain from sex during the study.

Inclusion Criteria

If you are a woman who could become pregnant, you need to have a negative pregnancy test within the 14 days before starting the study treatment.

I am using two birth control methods or am not having sex to avoid pregnancy during the study.

I have triple-negative breast cancer with remaining signs after chemotherapy.

Exclusion Criteria

I still have visible tumor or cancer cells at the surgery edge that weren't removed.

I have taken PARP inhibitors before radiation therapy.

I have never had radiation therapy on the same side breast or nearby lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Rucaparib is administered concurrently with a 6-week course of radiotherapy, followed by 4 additional weeks of maintenance rucaparib

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Radiotherapy
• Rucaparib

Trial Overview The trial tests Rucaparib combined with standard radiation therapy on patients with certain types of breast cancer that didn't fully respond to chemotherapy. The goal is to see if this drug plus radiation helps more than just radiation alone.

How Is the Trial Designed?

Group I: Rucaparib Administered With Radiation Experimental Treatment 2 Interventions

Treatment will consist of rucaparib at one dose level (300 mg BID, 400 mg BID, 500 mg BID or 600 mg BID) concurrently with a 6-week course of radiotherapy and 4 additional weeks of maintenance rucaparib at the same dose level. Radiotherapy will consist of 50 Gy in 2 Gy per fraction to the breast or chest wall with or without regional nodes plus a 10 Gy boost to the lumpectomy cavity, to a total dose of 60 Gy. A 10 Gy boost to the post-mastectomy scar is allowed at the discretion of the treating physician.

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

Approved in European Union as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in United States as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Published Research Related to This Trial

Ribociclib, a CDK4-6 inhibitor, has been approved as a first-line treatment for metastatic breast cancer, showing significant improvement in progression-free survival compared to endocrine therapy alone.

Preliminary data from five patients treated with ribociclib and palliative radiotherapy suggest a need for further investigation into the safety and efficacy of this combination, as ribociclib has a challenging toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer. Meattini, I., Desideri, I., Scotti, V., et al.[2022]

NanoOlaparib, a lipid-based formulation of the PARP inhibitor olaparib, significantly enhances the sensitivity of radiation-resistant prostate cancer cells and tumors, leading to improved tumor growth inhibition compared to traditional oral olaparib.

In a mouse model, combining NanoOlaparib with radiation not only tripled median survival time but also resulted in a complete response in half of the treated mice, indicating its potential as a powerful strategy for treating tumors with PTEN and TP53 deletions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation. van de Ven, AL., Tangutoori, S., Baldwin, P., et al.[2022]

Combining chemotherapy with radiation therapy has shown significant clinical advancements in cancer treatment, particularly through the use of systemic therapies that can enhance tumor control (radiosensitization) and reduce damage to healthy tissues (radioprotection).

Recent early-phase clinical trials have focused on identifying effective combinations of systemic agents with radiation, suggesting that using surrogate endpoints, like active drug metabolites in tumors, could help streamline the search for optimal treatment schedules, although more robust Phase III trials are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New and emerging radiosensitizers and radioprotectors. Spalding, AC., Lawrence, TS.[2007]

In the TRITON2 study involving 78 patients with metastatic castration-resistant prostate cancer (mCRPC) and non-BRCA DNA damage repair (DDR) gene alterations, limited responses to the PARP inhibitor rucaparib were observed, particularly in patients with ATM, CDK12, or CHEK2 alterations.

However, some patients with alterations in other DDR genes like PALB2, FANCA, BRIP1, and RAD51B showed potential benefits from PARP inhibition, suggesting that not all DDR alterations respond similarly to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. Abida, W., Campbell, D., Patnaik, A., et al.[2021]

In a study of 16 patients with hormone-receptor positive metastatic breast cancer receiving concurrent radiotherapy and CDK4/6 inhibitors (palbociclib or ribociclib), the treatment was generally well tolerated despite a high incidence of hematological toxicity, particularly neutropenia.

Neutropenia was observed in 31.2% of patients, with 25% experiencing grade 3 and 6.3% grade 4 toxicity; notably, many patients had a history of neutropenia from previous palbociclib cycles, indicating that prior toxicity may predict future risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: Preliminary assessment of toxicity. Ippolito, E., Greco, C., Silipigni, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4418389/

Benefits, risks, and safety of external beam radiation ... The Early Breast Cancer Trial Collaborative Group demonstrated that the addition of radiation reduced the 10-year risk of LRR from 25% to 8% and resulted in an ...

2. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/astro-corrects-media-misinformation-on-breast-cancer-treatment-options

ASTRO corrects media misinformation on breast cancer ... While acute skin toxicity is less severe with IORT compared to external beam radiation, long-term toxicity such as breast fibrosis is ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9272418/

Radiotherapy of Breast Cancer—Professional Guideline 1st ... Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (stage 0), as RT decreases the risk of local recurrence (LR) by 50– ...

4. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/first-randomized-study-comparing-proton-and-photon-radiation-therapy-for-breast-cancer-finds-both-pr

First randomized study comparing proton and photon ... Large phase III trial shows patients report excellent outcomes after either treatment, with differences in preference favoring protons.

5. mayoclinic.org mayoclinic.org/tests-procedures/radiation-therapy-for-breast-cancer/about/pac-20384940

Radiation therapy for breast cancer Radiation therapy is an effective way to reduce your risk of breast cancer recurring after surgery. In addition, it is commonly used to ease the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7136642/

Comparison of Toxicity and Cosmetic Outcomes After ... In women with breast cancer after BCS, APBI was associated with better cosmetic outcome and fewer acute and late radiation toxicities than WBI.

7. cancernetwork.com cancernetwork.com/view/exclusive-radiation-therapy-improves-qol-and-safety-outcomes-in-breast-cancer

Exclusive Radiation Therapy Improves QOL and Safety ... When compared with endocrine therapy, radiation therapy improved quality of life and adverse effects data, the phase 3 EUROPA study showed.