Niraparib + Neratinib for Ovarian Cancer
(iNNOVATE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Virginia Commonwealth University
Must not be taking: PPIs, P-gp substrates, CYP3A4 drugs
Disqualifiers: Invasive cancer, Cardiac disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
To determine the recommended phase 2 dose (RP2D) of niraparib and neratinib in combination in patients with advanced solid tumors during Phase 1. To evaluate clinical benefit (≥4-month progression-free survival \[PFS\]) of niraparib and neratinib in patients with platinum-resistant ovarian cancer in Phase 1b.
Will I have to stop taking my current medications?
The trial requires you to stop taking certain medications that might interact with the study drugs. You must stop using proton pump inhibitors 10 days before starting the trial and discontinue certain other medications at least 2 weeks prior. You can continue taking corticosteroids if your dose has been stable for at least 4 weeks before starting the trial.
What data supports the effectiveness of the drug Niraparib in treating ovarian cancer?
Niraparib has been shown to significantly extend the time patients live without their cancer getting worse when used as a maintenance treatment for ovarian cancer, especially after responding to platinum-based chemotherapy. It is effective regardless of specific genetic mutations, making it a promising option for many patients.12345
Is the combination of Niraparib and Neratinib safe for treating ovarian cancer?
What makes the drug combination of Niraparib and Neratinib unique for treating ovarian cancer?
The combination of Niraparib and Neratinib is unique because Niraparib is a PARP inhibitor that helps repair DNA damage in cancer cells, while Neratinib is a tyrosine kinase inhibitor that blocks signals promoting cancer cell growth. This dual approach targets different pathways in cancer cells, potentially offering a more comprehensive treatment strategy for ovarian cancer.12389
Research Team
Andrew Poklepovic, MD
Principal Investigator
Massey Cancer Center
Eligibility Criteria
Adults with advanced solid tumors, including ovarian cancer patients who are platinum-resistant and have had at least two prior therapies but no BRCA mutation. Participants must have adequate organ function, not be pregnant or breastfeeding, agree to use contraception, and cannot have certain health conditions like uncontrolled infections or recent major surgeries.Inclusion Criteria
I am 18 years old or older.
Agreement to abstain from activities that could result in pregnancy from screening through 90 days after the last dose of study treatment
Agreement to not donate blood during the study or for 90 days after the last dose of study treatment
See 13 more
Exclusion Criteria
My cancer has spread to my brain or its coverings.
Known hypersensitivity to study components or excipients
I cannot swallow pills.
See 16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase 1 Dose Escalation
Determine the recommended phase 2 dose (RP2D) of niraparib and neratinib using a modified 3+3 design
4 months
Regular visits for dose escalation and monitoring
Phase 1b Dose Expansion
Evaluate clinical benefit (≥4-month progression-free survival) of niraparib and neratinib in patients with platinum-resistant ovarian cancer
4 months
Regular visits for treatment and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 months
Treatment Details
Interventions
- Neratinib (Tyrosine Kinase Inhibitor)
- Niraparib (Poly (ADP-ribose) polymerase (PARP) inhibitor)
Trial OverviewThe trial is testing different doses of Niraparib and Neratinib to find the safest and most effective combination for treating advanced solid tumors. The focus is on determining the best dose during Phase 1 and assessing benefits in ovarian cancer patients during Phase 1b.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Phase 1b: Platinum Resistant Expansion CohortExperimental Treatment2 Interventions
This portion of the study provides for cohort expansion to observe for 4 month or greater progression-free survival in patients with platinum resistant ovarian cancer treated at the recommended phase 2 dose (RP2D) determined in Phase I.
Group II: Dose Level 4Experimental Treatment2 Interventions
Neratinib 240 mg and Niraparib 300 mg by mouth once daily for 28 day cycles.
Group III: Dose Level 3Experimental Treatment2 Interventions
Neratinib 240 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Group IV: Dose Level 2Experimental Treatment2 Interventions
Neratinib 200 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Group V: Dose Level 1Experimental Treatment2 Interventions
Neratinib 160 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Group VI: Dose Level -1Experimental Treatment2 Interventions
Neratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles.
Neratinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Nerlynx for:
- Extended adjuvant treatment of women with early-stage HER2-positive breast cancer
🇪🇺 Approved in European Union as Nerlynx for:
- Extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Virginia Commonwealth UniversityRichmond, VA
Loading ...
Who Is Running the Clinical Trial?
Virginia Commonwealth University
Lead Sponsor
Trials
732
Patients Recruited
22,900,000+
Puma Biotechnology, Inc.
Industry Sponsor
Trials
58
Patients Recruited
10,100+
GlaxoSmithKline
Industry Sponsor
Trials
4834
Patients Recruited
8,389,000+
Headquarters
London, UK
Known For
Vaccines & Medicines
Top Products
**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)
References
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 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.
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.
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: 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.
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.
Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. [2023]The aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer.
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.
Niraparib for the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. [2020]To review the efficacy and safety of niraparib for the treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC, FTC, and PPC).