Rucaparib + Radiation for Breast Cancer

Recruiting in Basking Ridge (>99 mi)

+8 other 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

31 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of a study drug called Rucaparib, administered in combination with the type of radiation therapy that is usually given to women with your form of breast cancer.

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.

What data supports the effectiveness of the drug Rucaparib combined with radiation therapy for breast cancer?

Research shows that combining PARP inhibitors, like Olaparib, with radiation can make cancer cells more sensitive to treatment, improving outcomes in certain cancers. This suggests that Rucaparib, another PARP inhibitor, might also enhance the effectiveness of radiation therapy in breast cancer. ^{1 2 3 4 5}

Is the combination of Rucaparib and Radiation therapy safe for humans?

Rucaparib has been studied for safety in humans, particularly in patients with ovarian and breast cancers with BRCA mutations. It is generally considered safe, but like many cancer treatments, it can have side effects. When combined with radiation therapy, it has shown potential in treating cervical cancer, suggesting it may be safe for use in combination with radiation, but more research is needed to confirm this for breast cancer specifically. ^{6 7 8 9 10}

What makes the Rucaparib + Radiation treatment for breast cancer unique?

Rucaparib + Radiation for breast cancer is unique because it combines a PARP inhibitor (Rucaparib) with radiation therapy, potentially enhancing the effectiveness of radiation by making cancer cells more sensitive to it. This combination is different from other treatments that typically use chemotherapy drugs or hormone therapies with radiation. ^{1 4 11 12 13}

Research Team

Atif Khan, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

Findings from Research

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]

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]

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]

References

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

New and emerging radiosensitizers and radioprotectors. [2007]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Combination of sunitinib, cetuximab and irradiation in an orthotopic head and neck cancer model. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer. [2022]

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

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation. [2022]

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

PARP Inhibitors for Cancer Therapy. [2022]

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

Breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1) restrict oral availability and brain accumulation of the PARP inhibitor rucaparib (AG-014699). [2021]

8. United States 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. [2021]

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

The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer. [2020]

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

Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. [2018]

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

Prospective results of concurrent radiation therapy and weekly paclitaxel as salvage therapy for unresectable locoregionally recurrent breast cancer. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: Preliminary assessment of toxicity. [2020]

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

Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer. [2015]