Niraparib for the Treatment of 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

Trial Summary

What is the purpose of this trial?

This trial tests whether niraparib can shrink tumors in patients with leiomyosarcoma. Niraparib stops cancer cells from repairing their damaged DNA, leading to their death. It targets patients with specific genetic changes in their cancer. Niraparib is an oral medication approved for maintenance treatment in various cancers including ovarian cancer.

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.

What data supports the effectiveness of the drug Niraparib (Zejula)?

Research shows that Niraparib is effective in extending the time patients with advanced ovarian cancer live without the disease getting worse, especially after responding to initial chemotherapy. It works for patients with specific genetic profiles and those without, making it a versatile option for maintenance therapy. ^{1 2 3 4 5}

Research Team

David Liebner, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

Interventions

• Niraparib

Participant Groups

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

Findings from Research

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 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]

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 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]

References

1. Germany 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. [2019]

2. France pubmed.ncbi.nlm.nih.gov

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

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

The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. [2023]