Niraparib + Selenium for Recurrent Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers, UGT1A1 inhibitors

Disqualifiers: Other active malignancy, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Trial Summary

Will I have to stop taking my current medications?

The trial requires stopping certain medications, including strong CYP3A4 inducers/inhibitors, UGT1A1 inhibitors, herbal medications containing selenium, vitamin E, and anticoagulants, at least 14 days before starting the trial. Check with the study team to see if your current medications fall into these categories.

What data supports the effectiveness of the drug Niraparib for recurrent ovarian cancer?

Research shows that Niraparib, a drug used for ovarian cancer, helps patients live longer without the disease getting worse. It has been shown to be effective in maintaining the health of patients who have responded to previous chemotherapy, regardless of specific genetic mutations. ^{1 2 3 4 5}

Is the combination of Niraparib and Selenium safe for humans?

Niraparib has been studied for safety in patients with ovarian cancer, showing that some people may need to reduce their dose due to side effects like low blood cell counts. The main safety concern is myelosuppression (a decrease in bone marrow activity leading to fewer blood cells), which can be managed by adjusting the dose. ^{1 2 6 7 8}

How is the drug Niraparib unique for treating recurrent ovarian cancer?

Niraparib is unique because it is a poly(ADP-ribose) polymerase inhibitor used as a maintenance treatment for recurrent ovarian cancer, helping to prolong the time patients remain free from disease progression after responding to platinum-based chemotherapy. It is effective regardless of BRCA mutation or homologous recombination deficiency status, making it a versatile option for many patients. ^{1 2 4 5 8}

What is the purpose of this trial?

This phase I/II trial tests the safety, side effects and best dose of a combination therapy (niraparib and selenium) in treating patients with BRCA negative ovarian cancer that has come back (recurrent) and does not respond to platinum based therapy (platinum resistant). Selenium is a form of the trace element with potential antineoplastic activity which may help block the formation of growths that may become cancer. Niraparib is in a class of medications called poly (ADP-ribose) polymerase inhibitors. It works by killing cancer cells and helps maintain the response of certain types of ovarian, fallopian tube and peritoneal cancers. Giving selenium and niraparib may kill more cells in patients with ovarian cancer.

Research Team

Lorna Rodriguez-Rodriguez

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults over 18 with recurrent BRCA negative ovarian cancer that's resistant to platinum therapy. Participants must have had no more than four prior chemo treatments, not be pregnant or breastfeeding, and agree to use effective birth control. They should have adequate organ function and blood counts, controlled blood pressure, and cannot have certain other medical conditions or recent treatments.

Inclusion Criteria

Aspartate aminotransferase (AST) =< 2.5 x ULN, unless liver metastases are present, in which case =< 5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

My kidney function, measured by creatinine levels or clearance, is within the required range.

Prothrombin (PT) =< 1.25 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

Exclusion Criteria

I have been diagnosed with MDS or AML.

I haven't taken any colony-stimulating factors in the last 4 weeks.

I have not taken UGT1A1 inhibitors in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Patients receive selenium intravenously and niraparib orally to assess safety, tolerability, and feasibility

8 weeks

Weekly visits for monitoring and dose adjustments

Dose-Expansion Treatment

Patients continue to receive selenium and niraparib to evaluate anti-tumor activity and tolerability

Up to 3 years

Monthly visits for imaging and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Bi-monthly visits for follow-up assessments

Treatment Details

Interventions

• Niraparib
• Selenium

Trial Overview The trial tests the safety and optimal dose of niraparib combined with selenium in treating patients whose ovarian cancer has returned and doesn't respond to platinum-based therapy. Niraparib is a PARP inhibitor which kills cancer cells; selenium may prevent growths from becoming cancerous.

Participant Groups

Group I: Treatment (selenium, niraparib) Experimental Treatment 5 Interventions

Patients receive selenium IV and niraparib PO on study. Patients also undergo CT, MRI, biopsy, and collection of blood samples throughout the trial.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

In a study of 553 patients with recurrent ovarian cancer, niraparib treatment led to a significant increase in mean progression-free survival (PFS) of 3.23 years for those with a germline BRCA mutation and 1.44 years for those without, compared to routine surveillance.

Niraparib also resulted in a greater time without symptoms or toxicity (TWiST), providing a benefit of 2.95 years for the gBRCAmut cohort and 1.34 years for the non-gBRCAmut cohort, indicating that patients experienced more time free from adverse effects compared to those receiving routine surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial. Matulonis, UA., Walder, L., Nøttrup, TJ., et al.[2020]

Niraparib significantly improves progression-free survival and other key outcomes in patients with recurrent, platinum-sensitive ovarian cancer, based on the phase III NOVA trial involving a randomized, double-blind, placebo-controlled design.

The treatment has a manageable safety profile, with most serious side effects being blood-related issues, which can be effectively managed through dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. Heo, YA., Duggan, ST.[2019]

In the ENGOT-OV16/NOVA trial, patients aged 70 and older with recurrent ovarian cancer who received niraparib showed significant progression-free survival (PFS) benefits, with non-gBRCAmut patients achieving a median PFS of 11.3 months compared to 3.8 months for those on placebo.

The safety profile of niraparib in older patients was similar to that in younger patients, with common adverse events being hematologic issues like thrombocytopenia and anemia, suggesting that niraparib is a viable treatment option for older patients with recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. Fabbro, M., Moore, KN., Dørum, A., et al.[2019]

Niraparib, a PARP inhibitor for recurrent ovarian cancer, showed no significant changes in its pharmacokinetics when taken with a high-fat meal compared to fasting, indicating it can be safely taken with or without food.

The study demonstrated that niraparib was well-tolerated and had similar adverse events regardless of the meal condition, confirming its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer. Moore, K., Zhang, ZY., Agarwal, S., 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, a treatment for recurrent ovarian cancer, has a high dose reduction rate of 68.9% due to treatment-emergent adverse events, with thrombocytopenia being a notable cause for 3.3% of patients.

Baseline body weight and platelet count are significant predictors for the risk of severe thrombocytopenia, suggesting that patients with a body weight under 77 kg or platelet count below 150,000/µl may benefit from starting at a lower dose of 200 mg/day without compromising progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. Berek, JS., Matulonis, UA., Peen, U., et al.[2021]

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. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. [2021]

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

Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial. [2020]

4. France pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. [2019]

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

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer. [2019]

7. France pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. [2021]