Niraparib + Dostarlimab for Recurrent Cervical Cancer

(STAR Trial)

Not currently recruiting at 3 trial locations

Overseen By Lead Gyn Onc, Nurse

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Must not be taking: Steroids, Immunosuppressants, PARP inhibitors

Disqualifiers: CNS metastases, Active infection, Autoimmune, 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: Unknown

Duration: Variable, as long as the tumor is not growing or spreading

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of combining two drugs, Niraparib and Dostarlimab, for treating recurrent or persistent cervical cancer. Researchers aim to assess both the positive and negative effects of this treatment on patients. Women diagnosed with cervical cancer that has returned or progressed after previous treatments may be suitable candidates for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic steroids or immunosuppressive therapy must be stopped 7 days before starting the trial, unless the dose is stable and low. It's best to discuss your specific medications with the trial team.

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

Research is examining the safety of combining niraparib and dostarlimab for treating recurring cervical cancer. Previous studies have shown that this combination can have both positive and negative effects on patients.

Niraparib is already used to treat some types of cancer and is generally well-tolerated. Dostarlimab has also undergone studies for safety and effectiveness. Both drugs have known side effects, which are often manageable. Common side effects include fatigue, nausea, and low blood cell counts.

In studies so far, researchers have closely monitored the combination of these two drugs to ensure patient safety. While more research is needed, evidence suggests that the treatment is generally well-tolerated with careful monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Niraparib and Dostarlimab for recurrent cervical cancer because these treatments offer a novel approach compared to traditional therapies. Niraparib is a PARP inhibitor, which works by preventing cancer cells from repairing their DNA, ultimately leading to their death. Dostarlimab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. While most existing treatments focus on chemotherapy or radiation, this combination targets the cancer in two innovative ways, potentially improving outcomes for patients with recurrent cervical cancer.

What evidence suggests that this combination treatment could be effective for recurrent cervical cancer?

Research has shown that using niraparib and dostarlimab together, as studied in this trial, might help treat recurrent cervical cancer. In one study, patients' cancer did not progress for about 3.8 months on average. These drugs stop cancer cells from repairing themselves and help the immune system fight the cancer. Early research suggests this combination could be beneficial, but further studies are needed to fully understand its advantages. ^{1 2 3 6 7}

Who Is on the Research Team?

Debra L. Richardson

Principal Investigator

Stephenson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with recurrent or progressive cervical cancer who have had at least one systemic treatment (excluding chemo with radiation). They must have measurable lesions, stable corticosteroid doses if applicable, good organ function, and an ECOG status of 0-1. Exclusions include active CNS metastases, recent transfusions, certain blood disorders, HIV/Hepatitis B/C infections, recent investigational drug use or major surgery.

Inclusion Criteria

I agree not to donate blood during the study or for 90 days after the last treatment.

Patient has measurable lesions by RECIST v1.1

If of childbearing potential, has a negative pregnancy test within 7 days prior to taking study medication or agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment, or be of non-childbearing potential

Exclusion Criteria

I have not received a live vaccine in the last 14 days.

I have not had active treatment for another cancer, except skin cancer, in the last 2 years.

I have not been in a clinical trial for a new treatment or device within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Niraparib daily and dostarlimab by vein every three weeks for 4 cycles then every six weeks

Variable, as long as the tumor is not growing or spreading

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• Niraparib

Trial Overview The study tests the safety and effects of combining Niraparib and dostarlimab in treating cervical cancer that has come back or worsened. Participants will receive both drugs to determine how well they work together against this type of cancer.

How Is the Trial Designed?

Group I: Niraparib + dostarlimab Experimental Treatment 2 Interventions

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

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Published Research Related to This Trial

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

The combination treatment of dostarlimab and niraparib in patients with recurrent platinum-resistant ovarian cancer showed a low objective response rate of only 7.3%, leading to the early termination of the study due to insufficient efficacy.

Despite the treatment being generally safe with no new safety issues identified, 95.1% of patients experienced treatment-related adverse events, and health-related quality of life worsened over time, indicating a need for more effective therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Randall, LM., O'Malley, DM., Monk, BJ., et al.[2023]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

In a phase 3 trial involving 494 patients with advanced or recurrent endometrial cancer, dostarlimab combined with chemotherapy significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 61.4% survival rate at 24 months compared to 15.7% for placebo.

Overall survival at 24 months was also better with dostarlimab (71.3%) compared to placebo (56.0%), indicating its efficacy as a treatment option, although it was associated with a higher incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. Mirza, MR., Chase, DM., Slomovitz, BM., et al.[2023]

Niraparib (Zejula) is effective for treating recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, providing a targeted therapy option for these specific cancer types.

Ocrelizumab (Ocrevus) has shown efficacy in managing both relapsing and primary progressive multiple sclerosis, while dupilumab (Dupixent) is effective for patients with moderate-to-severe atopic dermatitis, highlighting its role in managing chronic inflammatory skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Citations

1. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/6/939/762896/Phase-II-Study-Evaluating-the-Efficacy-of

Phase II Study Evaluating the Efficacy of Niraparib and ... The secondary endpoints of PFS and OS are shown in Fig. 2. At a median follow-up of 10.13 months, the median PFS was 3.8 months (95% CI, 1.63–NA) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04068753

Niraparib in Combination With Dostarlimab in Patients With ... The purpose of this research study is to test the safety of Niraparib and dostarlimab as a combination treatment and see what effects (good and bad) this ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-01721

Niraparib and Dostarlimab for the Treatment of Recurrent ... This phase II trial studies how well niraparib and dostarlimab work for the treatment of cervical cancer that has come back (recurrent) or is growing, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05870761

Study Details | NCT05870761 | Combination Niraparib and ... This phase II trial tests how well niraparib and dostarlimab work in treating patients with uterine serous carcinoma that has come back (after a period of ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.5574

Phase II trial assessing niraparib with or without ... Niraparib as single agent for treatment in a PlatR enriched recurrent EC population showed modest activity with clinical benefit rate at 16w of 20%.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05126342?term=AREA%5BSponsorSearch%5D(COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22AGO%20Research%20GmbH%22))&rank=3

Study to Estimate Efficacy of Combining Dostarlimab and ... This is a multicenter, open-label, non-randomized pilot study (Phase II). The aim is to obtain evidence of efficacy of niraparib and dostarlimab (TSR-042) ...

7. aacrjournals.org aacrjournals.org/cancerrescommun/article-pdf/doi/10.1158/2767-9764.CRC-25-0192/3606559/crc-25-0192.pdf

Phase II study evaluating the efficacy of niraparib and ... Phase II study evaluating the efficacy of niraparib and dostarlimab (TSR-042) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients.