Genetic Profile-Guided Therapy for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University Health Network, Toronto
Must not be taking: Investigational drugs
Disqualifiers: Hypertension, Brain metastases, Autoimmune, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this research study is to see how useful it is to look at biomarkers in the blood and tumor tissue of participants with ovarian, fallopian tube or primary peritoneal cancer who have previously received treatment with a drug called a PARP inhibitor, and using the results to determine the best treatment for these participants. Biomarkers are molecules such as genes (molecules that contain instructions for the development and function of cells in the body) and proteins that may be used to see how well a body responds to certain treatments.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken an investigational drug (other than a PARP inhibitor) within 30 days or a PARP inhibitor within 14 days before starting the study treatment.
What data supports the effectiveness of the drug combination including Niraparib for ovarian cancer?
Research shows that Niraparib, a drug in the treatment plan, helps extend the time patients with ovarian cancer live without the disease getting worse, especially after initial chemotherapy. It is effective for patients with or without specific genetic mutations.
12345Is niraparib safe for use in humans?
Niraparib is generally well tolerated in humans, with the main safety concern being myelosuppression (a decrease in bone marrow activity leading to fewer blood cells). This side effect is manageable with monitoring and dose adjustments based on weight and platelet count.
678910How is the drug Niraparib unique in treating ovarian cancer?
Niraparib is unique because it is a PARP inhibitor that can be used as maintenance therapy for ovarian cancer patients who have responded to platinum-based chemotherapy, regardless of their BRCA mutation or homologous recombination deficiency status. This makes it a versatile option for patients with limited maintenance treatment choices.
457811Eligibility Criteria
This trial is for patients with ovarian, fallopian tube, or primary peritoneal cancer who have relapsed after PARP inhibitor therapy. They must have a good heart function, measurable disease by RECIST 1.1 criteria, and proper organ function. Women of childbearing potential need to use effective contraception and not breastfeed during the study.Inclusion Criteria
I agree not to donate blood during and for 3 months after the study.
Patient must agree to not breastfeed during the study or for 30 days after the last dose of study treatment
My cancer has returned after treatment, regardless of how many treatments I've had.
+10 more
Exclusion Criteria
I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.
I have not had major chest or belly surgery in the last 2 weeks or any unhealed surgical cuts.
I don't have lasting side effects from cancer treatment worse than mild.
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Biomarker Testing
Blood and tumor tissue samples are collected for biomarker testing to determine the participant's molecular profile
3 weeks
1 visit (in-person)
Initial Treatment
Participants receive bevacizumab and niraparib for 3 cycles, each cycle being 21 days
9 weeks
3 visits (in-person)
Cohort-Specific Treatment
Participants are assigned to a cohort based on genetic testing results and receive a combination of study drugs until disease progression or discontinuation criteria are met
Up to 1 year
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial tests if using genetic markers from blood and tumor tissue can guide treatment choices post-PARP inhibitors in cancers like ovarian cancer. It involves drugs Niraparib, Dostarlimab, Bevacizumab, Paclitaxel to see which works best based on these biomarkers.
3Treatment groups
Experimental Treatment
Group I: Initial/Cohort CExperimental Treatment2 Interventions
Niraparib by mouth (orally), once a day, every day. Bevacizumab, by vein (intravenously), once every 3 weeks for up to 1 year, then every 6 weeks.
Group II: Cohort BExperimental Treatment3 Interventions
Paclitaxel, by vein (intravenously), once a week. Bevacizumab, by vein (intravenously), once every 3 weeks for up to 1 year, then every 6 weeks.
Dostarlimab, by vein (intravenously), once every 3 weeks for 4 doses, then every 6 weeks afterwards.
Group III: Cohort AExperimental Treatment3 Interventions
Niraparib by mouth (orally), once a day, every day. Bevacizumab, by vein (intravenously), once every 3 weeks for up to 1 year, then every 6 weeks.
Dostarlimab, by vein (intravenously), once every 3 weeks for 4 doses, then every 6 weeks afterwards.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Princess Margaret Cancer CentreToronto, Canada
Loading ...
Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
GlaxoSmithKlineIndustry Sponsor
References
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. [2019]Label="BACKGROUND">Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.
OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. [2022]To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.
The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China. [2021]Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China.
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. [2022]Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.
Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects. [2023]In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA-mutated (non-gBRCAm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gBRCAm cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA-mutated (sBRCAm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or BRCA wild-type (BRCAwt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with BRCAwt tumors with other non-BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with BRCAwt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with BRCAwt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sBRCAm, other non-BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA/HRR mutation status or myChoice CDx GIS.
Niraparib for the treatment of ovarian cancer. [2019]Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA). Overall, niraparib is well tolerated and its toxicities, primarily hematologic, are manageable especially with recently released initial dose modification guidelines based on weight and baseline platelet count. The role of niraparib as maintenance following frontline platinum-based chemotherapy as well as in the treatment of recurrent high-grade serous ovarian cancer is an active area of investigation. Areas covered: This review focuses on niraparib, its pharmacology, clinical efficacy, and adverse effects as evidenced by prospective clinical trials, and licensed indications. Expert commentary: Niraparib introduced the use of PARP inhibitors regardless of biomarker status. Recent studies highlight the critical need for more accurate biomarkers to identify patients most likely to benefit from treatment with PARP inhibitors. In the next 5 years, we anticipate further expansion of and elucidation regarding the optimal indication for use of niraparib in the treatment of ovarian cancer.
Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]Niraparib (Zejula™) is a poly(ADP-ribose) polymerase inhibitor recently approved by the US Food and Drug Administration for the maintenance treatment of patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. The pivotal phase III clinical trial has shown improved progression-free survival in patients receiving niraparib compared with those receiving placebo.
Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]Niraparib (Zejula™) is a PARP inhibitor which is approved for maintenance therapy in adults with advanced ovarian cancer in complete or partial response to platinum-based chemotherapy. In a placebo-controlled phase III trial in patients with newly diagnosed advanced ovarian cancer, niraparib significantly extended progression free survival in two predefined populations, namely a patient population with altered homologous-recombination DNA repair pathways [i.e. homologous-recombination deficiency positive (HRd)] and the overall trial population. A prespecified exploratory subgroup analysis indicated that niraparib was also efficacious in patients who were homologous recombination deficiency negative or homologous recombination proficient (HRp). Niraparib has a manageable tolerability profile with myelosuppression as the main safety concern. Haematological reactions were managed with monitoring and dose reduction or interruption. A weight- and platelet count-based individualised dosage regimen introduced during the trial (and subsequently approved) appeared to improve haematological tolerability. Niraparib is a useful option for first-line maintenance therapy for advanced ovarian cancer in adults who responded to platinum-based chemotherapy, regardless of homologous-recombination deficiency status and is a promising option for HRp patients, for whom maintenance treatment options are limited.
Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. [2021]To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Niraparib and Advanced Ovarian Cancer: A Beacon in the Non-BRCA Mutated Setting. [2023]Ovarian cancer (OC) is the eighth most common cancer among the female population and the most lethal of all the female reproductive system malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPis) have reshaped the treatment scenario of metastatic OC in the maintenance setting post platinum-based chemotherapy. Niraparib is the first Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved PARPi as maintenance therapy for platinum-sensitive OC, regardless of BReast CAncer gene (BRCA) status, in first-line patients, with a recent restriction to germline BRCA mutations in second-line patients. In this review, we comprehensively summarized the pharmacological properties of niraparib, alongside the efficacy and safety data of the main trials leading to the current approvals, and discussed the future development of this agent.
Niraparib: A Review in Ovarian Cancer. [2019]Niraparib (Zejula®), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Approval was based on the results of the randomized, double-blind, placebo-controlled phase III NOVA trial. In NOVA, niraparib significantly prolonged progression-free survival (primary endpoint), chemotherapy-free interval and time to first subsequent therapy compared with placebo in patients with recurrent, platinum-sensitive, high grade serous ovarian, fallopian tube or primary peritoneal cancer. The beneficial effects of niraparib were consistent regardless of BRCA mutation or homologous recombination deficiency (HRD) status. Niraparib had a manageable tolerability profile, with the majority of grade 3 or 4 adverse events being haematologic abnormalities (e.g. thrombocytopenia, anaemia, neutropenia). Adverse events were generally well managed with dose interruption or modification of niraparib. Current evidence suggests that niraparib is an effective new option with a manageable tolerability profile for the maintenance treatment of recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults, with or without BRCA1/2 mutation or HRD.