Niraparib for Leiomyosarcoma

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: PARP inhibitors, Anti-estrogens

Disqualifiers: MDS, AML, CNS metastases, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 15 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called niraparib to determine if it can shrink tumors in people with leiomyosarcoma, a type of cancer. Niraparib is a targeted therapy that blocks a protein cancer cells use for repair, potentially causing cell death. Suitable candidates for this trial have a confirmed diagnosis of leiomyosarcoma, advanced or metastatic disease that cannot be surgically removed, and have tried at least one other cancer treatment without success. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop taking non-steroidal anti-estrogen agents at least two weeks before starting the study. If you are on corticosteroids, you can continue as long as the dose is stable for at least four weeks before starting the trial.

Is there any evidence suggesting that niraparib is likely to be safe for humans?

Research has shown that niraparib, a PARP inhibitor, has been studied for other conditions, and its safety profile is well-known. In earlier studies, over 10% of patients experienced common side effects such as nausea and tiredness. However, long-term safety data from studies like NOVA indicate that niraparib is generally well-tolerated when doses are adjusted correctly.

In the PRIMA study, some patients needed dose adjustments due to side effects, with temporary dose pauses occurring in about 79.5% of cases and dose reductions in 70.9%. Despite this, no new safety concerns emerged over a follow-up period of 6.2 years.

Overall, while niraparib can cause some side effects, dose adjustments often manage these effectively. The treatment appears to maintain a stable safety record over time. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Niraparib is unique because it works as a PARP inhibitor, targeting a specific enzyme that cancer cells need to repair their DNA. This is different from the usual chemotherapy treatments for leiomyosarcoma, which often attack rapidly dividing cells in a more generalized way. Researchers are excited about Niraparib because its targeted approach may lead to fewer side effects and more effective treatment for patients with this type of cancer. By honing in on the cancer cells' repair mechanisms, Niraparib has the potential to deliver more precise and powerful results.

What evidence suggests that niraparib might be an effective treatment for leiomyosarcoma?

Research shows that niraparib, a type of medication, can treat certain cancers by preventing cancer cells from repairing damaged DNA, leading to their death. Studies have found that niraparib can more than double the time patients live without their cancer worsening compared to a placebo, particularly in patients with specific genetic traits related to DNA damage. In everyday use, patients taking niraparib have experienced longer periods without disease progression, and the treatment is generally well-tolerated. While these results are promising for cancers like ovarian cancer, its effectiveness for leiomyosarcoma remains under investigation. Participants in this trial will receive niraparib to further evaluate its impact on leiomyosarcoma. ^{6 7 8 9 10}

Who Is on the Research Team?

David Liebner, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Inclusion Criteria

Platelets >= 100,000/uL

Hemoglobin >= 9 g/dL

Participant must have histologically documented LMS. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study.

Exclusion Criteria

You should not have any known allergies or hypersensitivity to the ingredients in niraparib.

Participant must not be simultaneously enrolled in any interventional clinical trial

Participant must not have had major surgery =< 4 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib orally once daily. Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity.

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib

How Is the Trial Designed?

Group I: Treatment (Niraparib) Experimental Treatment 1 Intervention

Patients receive niraparib PO QD. Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

David Liebner, MD

Lead Sponsor

Trials

1

Published Research Related to This Trial

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]

Niraparib has been approved by the FDA for patients with complete or partial response to first-line platinum-based chemotherapy, regardless of their BRCAm or HRD status, expanding treatment options for more patients.

Olaparib, in combination with bevacizumab, has also received FDA approval for patients with epithelial ovarian cancer, indicating that PARP inhibitors are now beneficial not only for BRCAm and HRD-deficient patients but also for those with HRD-proficient tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. Washington, CR., Moore, KN.[2023]

Niraparib is an FDA and EMA-approved oral PARP inhibitor for maintenance treatment in women with recurrent ovarian cancer who have responded to platinum-based chemotherapy, showing efficacy in both BRCA mutated and wild-type cancers.

While niraparib is effective, it can cause significant hematologic toxicities, such as thrombocytopenia and anemia, necessitating dose adjustments for certain patients to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. Moore, KN., Mirza, MR., Matulonis, UA.[2019]

Niraparib significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[2022]

Citations

1. zejulahcp.com zejulahcp.com/efficacy/

PRIMA Clinical Study | Efficacy | ZEJULA (niraparib) for HCPs Primary Analysis · The PRIMA trial met its primary endpoint: ZEJULA more than doubled median PFS vs placebo in the HRD-positive population · Primary analysis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10259665/

Real‐world outcomes of niraparib treatment in patients with ... These results revealed that niraparib was well tolerated in real‐world settings, which may be due to the intense follow‐up and flexible ...

3. facingourrisk.org facingourrisk.org/XRAY/PARP-inhibitor-ovarian-cancer-survival

Niraparib improves outcomes in patients with newly ... The results of this trial showed that treatment with niraparib provides longer progression-free survival than placebo for the overall patient population.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663182/

Efficacy and Safety of Niraparib as First-Line Maintenance ... The results of HRD testing revealed that 66 (33.2%) patients were positive, 52 (26.1%) negative, and 81 (40.7%) not known. It is noteworthy that ...

5. zejula.com zejula.com/about/clinical-trial-results/

Clinical Trial Results | ZEJULA (niraparib) ZEJULA has been studied in a trial called PRIMA, which measured median progression-free survival, or mPFS, in patients who tested positive for HRD.

6. gskpro.com gskpro.com/en-ie/products/zejula/safety/

Safety in PRIMA | Zejula (niraparib tosylate monohydrate) In PRIMA, adverse events led to dose interruptions and dose reductions in 79.5% and 70.9% of patients who received ZEJULA, respectively.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/208447s014lbl.pdf

ZEJULA® (niraparib) - accessdata.fda.gov The most common adverse reactions in >10% of 830 patients who received ZEJULA in the NOVA and QUADRA trials (n = 830) were nausea (70%), fatigue (58%), ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10313963/

Safety and management of niraparib monotherapy in ... Long-term safety data from the NOVA trial confirmed that niraparib is well tolerated with appropriate dose modifications.

9. zejulahcp.com zejulahcp.com/

Ovarian Cancer Treatment | ZEJULA (niraparib) for HCPs Individualized starting dose gives your patients a tailored dose. · View the Efficacy Data · Safety Profile · Dosing · INDICATION & IMPORTANT SAFETY INFORMATION.

10. zejulahcp.com zejulahcp.com/safety/

Safety & Side Effects| ZEJULA (niraparib) for HCPs Long-term Safety Data. In PRIMA, no new safety signals were reported in the 6.2-year median follow-up5,6. TEAE overview from 6.2-year follow-up of the HRD ...