Niraparib + TSR-042 for Endometrial Cancer

Not currently recruiting at 7 trial locations
Age: 18+
Sex: Female
Trial Phase: Phase 2
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, niraparib (a PARP inhibitor) and TSR-042 (dostarlimab, an immunotherapy drug), can benefit individuals with advanced endometrial cancer that has recurred after treatment. The study examines the potential benefits of blocking a specific protein for patients with this cancer type. Individuals whose endometrial cancer worsened after treatment and who have tried at least one type of platinum-based chemotherapy may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop chemotherapy or biologic agents 4 weeks before starting, and hormonal therapy 2 weeks before starting. If you're on corticosteroids, you can continue as long as your dose is stable for at least 4 weeks before starting the trial.

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

Research shows that the combination of niraparib and TSR-042 (dostarlimab) is being tested for safety and effectiveness in treating advanced endometrial cancer. Previous studies found that this combination can significantly extend the time before the cancer worsens.

Regarding safety, past studies showed that this combination is generally well-tolerated by patients. However, like many cancer treatments, some side effects have been reported, including tiredness, nausea, and low blood cell counts. Patients should discuss potential side effects with their doctor, as reactions to treatment can vary.

Overall, research suggests that the combination of niraparib and TSR-042 is promising in terms of safety, but individual experiences may differ.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about Niraparib + TSR-042 for endometrial cancer because it offers a novel approach compared to standard treatments like chemotherapy, surgery, and radiation. Niraparib is a PARP inhibitor that works by interfering with cancer cell DNA repair, potentially leading to cancer cell death. TSR-042 (also known as dostarlimab) is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination targets both the cancer cells directly and boosts the body's immune response, which could lead to improved outcomes for patients.

What evidence suggests that niraparib and TSR-042 could be effective for endometrial cancer?

Research has shown that using niraparib with TSR-042 (dostarlimab) may help treat endometrial cancer. In this trial, participants will receive this combination treatment. One study found that this combination significantly increased the time patients lived without their cancer worsening, specifically for those with advanced or recurrent endometrial cancer. This suggests these drugs might slow or stop cancer growth. Another study demonstrated some positive effects, indicating potential benefits in cancer treatment. Overall, these treatments show promising results for people with advanced stages of this cancer.13678

Who Is on the Research Team?

AM

Amit M Oza, M.D.

Principal Investigator

UHN - Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for patients with advanced or recurrent endometrial cancer who have had at least one platinum-based chemotherapy. They must show disease progression, have a performance status ≤ 2, and measurable disease. Exclusions include those with certain medical conditions like fistulas, lung diseases, recent transfusions or surgeries, MDS/AML history, bowel obstruction within 3 months, immunodeficiency including HIV/Hepatitis B/C active infections, brain metastases unless stable over 28 days without steroids needed for control of symptoms.

Inclusion Criteria

My organs and bone marrow are functioning normally.
I have been on a stable dose of corticosteroids for at least 4 weeks.
I can take care of myself and am up and about more than half of my waking hours.
See 7 more

Exclusion Criteria

I have not taken hormonal therapy in the last 2 weeks.
My brain metastases have been stable for a set period.
I have been treated with PARP inhibitors or drugs targeting DNA repair.
See 18 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib monotherapy or in combination with TSR-042. Niraparib is taken daily, and TSR-042 is administered intravenously on specific days of the cycle.

21-day cycles, up to 2 years
Visits on Days 1, 8, 15 of Cycle 1; Days 1 and 15 from Cycle 2 onward

End of Study Treatment

Participants undergo tests and procedures for safety purposes after discontinuing study treatment.

Follow-up

Participants are monitored for side effects and undergo radiological assessments every 8 weeks until disease progression. Follow-up for side effects is weekly for the first 4 weeks, then monthly until resolution.

5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Niraparib
  • TSR-042
Trial Overview The study tests niraparib in combination with TSR-042 to see if blocking the PARP protein can benefit those with recurrent endometrial cancer. It also examines how PTEN gene loss affects treatment response. This phase 2 trial will assess clinical benefits and potentially pave the way for new therapeutic strategies.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Niraparib +TSR-042Experimental 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?

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+

Tesaro, Inc.

Industry Sponsor

Trials
57
Recruited
10,600+

Citations

Phase II Study Evaluating the Efficacy of Niraparib and ...We designed a single-arm, open-label, phase II clinical trial to evaluate the combination of niraparib and dostarlimab in patients with R/M HNSCC.
Clinical outcome and biomarker assessments of a multi- ...In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.
Findings From Cohort A of the OPAL Phase II TrialIn this phase II study, the triplet combination of niraparib-dostarlimab-bevacizumab resulted in a confirmed investigator-assessed 17.1% ORR.
Jemperli (dostarlimab) plus Zejula (niraparib) combination ...Jemperli (dostarlimab) plus Zejula (niraparib) combination significantly improved progression-free survival in primary advanced or recurrent endometrial cancer.
Dostarlimab Plus Chemotherapy Opens Doors Across ...On August 1, 2024, the FDA approved dostarlimab plus carboplatin and paclitaxel followed by single-agent dostarlimab maintenance therapy.
Dostarlimab/Chemo/Niraparib Generates PFS Benefit in ...Dostarlimab/chemotherapy/niraparib elicited favorable PFS outcomes across several subgroups in primary advanced or recurrent endometrial cancer.
Dostarlimab/Niraparib Improves PFS Outcomes in ...Dostarlimab/Niraparib Improves PFS Outcomes in Advanced Endometrial Cancer ... Data from part 2 of the phase 3 RUBY trial support the use of ...
Phase III Trial Data Show Meaningful Survival ...In the overall patient population, Jemperli plus Zejula produced a statistically significant 40% decrease in the risk of disease progression or ...
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