Niraparib + Radiotherapy for Triple Negative Breast Cancer

(UNITY Trial)

Not currently recruiting at 1 trial location
Alice Ho, MD profile photo
Overseen ByAlice Ho, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Massachusetts General Hospital
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of Niraparib, an oral medication, combined with radiation therapy to determine its effectiveness in treating triple negative breast cancer (a type of breast cancer lacking three common receptors). The goal is to assess whether this combination can manage or reduce the cancer. The trial seeks participants who have undergone surgery for triple negative breast cancer but still have some invasive disease. Participants should plan to receive radiation therapy and must stop other cancer treatments before starting this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

Will I have to stop taking my current medications?

You will need to stop taking any cytotoxic chemotherapy, immunotherapy, and biologic therapy at least 2 weeks before starting the trial. However, you can continue taking corticosteroids if your dose has been stable for at least 4 weeks before starting the trial.

Is there any evidence suggesting that Niraparib and Radiation Therapy are likely to be safe?

Studies have shown that Niraparib is generally well-tolerated by patients with various types of cancer, including breast cancer. In past research, patients taking Niraparib for breast cancer, including those with triple-negative breast cancer, experienced some side effects, which were mostly manageable. Common side effects included tiredness, nausea, and low blood cell counts, while serious problems were uncommon.

Research also shows that combining Niraparib with other treatments, such as pembrolizumab, has yielded promising results in fighting cancer while maintaining safety. Since this trial is in the early phase, it primarily focuses on ensuring the treatment's safety for participants. Niraparib is already FDA-approved for other conditions, suggesting some confidence in its safety. However, each study is unique, so monitoring for any new findings as the trial progresses is important.12345

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

Unlike the standard treatments for triple-negative breast cancer, which typically involve chemotherapy, Niraparib is a PARP inhibitor that targets the DNA repair process in cancer cells, making it harder for them to survive. This mechanism of action is particularly exciting because it has the potential to enhance the effectiveness of concurrent radiation therapy, a common component in cancer treatment. Researchers are hopeful that combining Niraparib with radiation could lead to better outcomes by specifically attacking cancer cells while sparing healthy ones, potentially reducing side effects and improving patient quality of life.

What evidence suggests that Niraparib combined with radiotherapy could be an effective treatment for triple negative breast cancer?

Research has shown that Niraparib, a drug tested in this trial for triple negative breast cancer, yields promising results. In one study, patients who took Niraparib with pembrolizumab showed a strong reduction in tumor size, including those with advanced cancer. Another study found that after two rounds of Niraparib, about 90.5% of patients experienced at least a 30% reduction in tumor size. These findings suggest that Niraparib could help reduce tumors in patients with triple negative breast cancer. In this trial, Niraparib will be administered alongside Radiation Therapy to evaluate its effectiveness.23467

Who Is on the Research Team?

ABR

Alice Ho, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with non-metastatic triple negative breast cancer who've had surgery and are planning postoperative radiation therapy. They must have some remaining invasive disease, not be pregnant or breastfeeding, agree to contraception use, and have good organ function. Exclusions include prior PARP inhibitor treatment, certain small tumors, significant other diseases or unresolved toxicities from past treatments.

Inclusion Criteria

I still have cancer after chemotherapy, or my tumor is at least 1.0 cm without chemotherapy.
I can swallow and keep down pills.
Participant must agree not to breastfeed during the study or for 30 days after the last dose of study treatment
See 12 more

Exclusion Criteria

I have not had any other cancer in the last 5 years.
I have a history of MDS or AML.
I have not had cancer treatments for at least 2 weeks and any side effects have gone.
See 17 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Niraparib is administered orally on a daily basis, concurrently with radiation therapy

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

  • Niraparib
  • Radiation Therapy
Trial Overview The study tests Niraparib given alongside standard postoperative radiation therapy in patients with triple negative breast cancer. It aims to see if this combination can improve outcomes compared to radiation alone.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: NiraparibExperimental Treatment2 Interventions

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

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Approved in European Union as Zejula for:
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Approved in United States as Zejula for:
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Approved in Canada as Zejula for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials
3,066
Recruited
13,430,000+

Tesaro, Inc.

Industry Sponsor

Trials
57
Recruited
10,600+

Published Research Related to This Trial

Triple-negative breast cancer is a diverse and aggressive type of cancer, and while molecular characterization isn't standard practice, it can help in understanding the disease better and predicting outcomes.
Recent advances in treatment options include neoadjuvant platinum-based chemotherapy and targeted therapies for patients with BRCA mutations, which may improve outcomes in various stages of the disease.
Advances in the systemic treatment of triple-negative breast cancer.Lebert, JM., Lester, R., Powell, E., et al.[2023]
Niraparib, a PARP inhibitor, significantly improves progression-free survival in patients with advanced epithelial ovarian cancer, but nearly all patients (≥99%) experience treatment-emergent adverse events, with 51-74% experiencing severe (grade ≥3) events.
An individualized starting dose of niraparib based on body weight and platelet count leads to fewer severe adverse events and dose modifications, suggesting a tailored approach can enhance safety while maintaining treatment efficacy.
Safety and management of niraparib monotherapy in ovarian cancer clinical trials.Monk, BJ., González-Martin, A., Buckley, L., et al.[2023]
Niraparib, a PARP inhibitor, significantly increased median survival and reduced tumor burden in a specific BRCA-mutant TNBC mouse model (MDA-MB-436), demonstrating its potential efficacy against brain metastases of triple-negative breast cancer.
The study found that combining RAD51 inhibition with PARP inhibition could enhance the sensitivity of various TNBC cell lines to treatment, suggesting a promising strategy for improving therapeutic outcomes in this challenging cancer type.
Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wild-type intracranial triple-negative breast cancer murine models.Sambade, MJ., Van Swearingen, AED., McClure, MB., et al.[2022]

Citations

A Phase I Study of Adjuvant Niraparib Administered ...Residual disease after neoadjuvant therapy (NAT) is associated with higher risk of recurrence, including local failure (25%) in triple ...
Neoadjuvant study of niraparib in patients with HER2- ...After 2 cycles, tumor response (≥30% reduction from baseline) by MRI was 90.5% and 40.0% (6 of 15) of patients who received only niraparib (2–6 cycles) had ...
Open-label Clinical Trial of Niraparib Combined With ...Combination niraparib plus pembrolizumab offers promising antitumor activity in patients with advanced or metastatic triple-negative breast cancer.
Study Details | NCT04915755 | Efficacy and Safety ...This study will assess the efficacy and safety of Niraparib in participants with either tumor mutation in the BRCA gene (tBRCAmut) HER2- breast cancer ...
TOPACIO/Keynote-162: Niraparib + pembrolizumab in ...Ten of 13 responders have ongoing responses; 13 pts have received > 6 mos of treatment (6 BRCAmut, 5 BRCAwt, 2 BRCAunk); 11 pts remain on ...
A phase 1 evaluation of the safety and tolerability ...Phase 1 trial to determine the safety and tolerability of everolimus and niraparib in patients with advanced ovarian and breast malignancies ...
Triple negative breast cancer: Pitfalls and progressOpen-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer.
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