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Table 4 Clinical trials of niraparib for cancer patient with different histological subtypes

From: PARP inhibitors as potential therapeutic agents for various cancers: focus on niraparib and its first global approval for maintenance therapy of gynecologic cancers

Description of Study participants Phases Methods Observed outcomes (primary and/or secondary) References
Hundred patients with advanced solid tumors in three sites ((dose escalation study) phase I Two cohort studies with single arm in each
Part A: 60 patients
 • enriched for BRCA1 and BRCA2 mutation carriers
 • received niraparib daily at ten escalating doses from 30 mg to 400 mg in a 21-day cycle to establish the maximum tolerated dose
Part B: 40 patients
 • sporadic platinum-resistant HGSOC and sporadic prostate cancer
 • investigating the maximum tolerated dose
- maximum tolerated dose is 300 mg/day dose liming toxic effects (Initial cycle)
- Grade 3 fatigue (30 mg/day) and pnemonitis (60 mg/day) were observed during first cycle
- Grade 4 thrombocytopenia (400 mg/day)
- Other common treatment related grade 1 and 2 side effects
- Inhibition of PARP exceeds 50% at dose greater than 80 mg/day (80 mg > ED50)
- Antitumor effect was observed beyond 60 mg/day
Patients with sporadic CRPC Phase I randomized clinical trial with two treatment arms (21 patients)
‑ Arm 1: niraparib 290–300 mg/day
‑ Arm 2: placebo
- Stabilization of CRPC
- in 43% of patients with a median duration of response of 254 days
- 30% of patients had a decrease of circulating tumor cells
- No correlation between ERG rearrangements/loss of PTEN expression and treatment response.
Patients with recurrent OC (553 patients) phase III Randomized double blind clinical trial with two category ad two arms per category
- Arm 1: Niraparib 300 mg once daily
 • 138 patients
- Arm 2: placebo
 • 65 patients
➢ Both arm 1 and 2 patients are with gBRCA mutant tumors
- Arm 3: Niraparib 300 mg once daily
 • 234 patients
- Arm 4: Placebo
 • 116 patients
➢ Both arm 3 and 4 patients are with non-gBRCA mutant (wild type) tumors irrespective of HR status
The primary outcomes were PFS
In gBRCA cohort
 • (21 months vs. 5.5 months for treatment to placebo)
For non-gBRCA cohort with HRD positivity
 • The PFS was found to be 12.9 and 3.8 months for niraparib and placebo arms, respectively.
Overall PFS in non-gBRCa cohor
 • 9.3 months vs 3.9 months
181 patients with recurrent OC, no prior use PARP inhibitors and at least 2 previous platinum therapy Phase III Randomized double blind clinical trial (two cohorts based on gBRCA status) Platinum resistance rates were 42%, 53% and 49% for gBRCA, non-gBRCA and pooled cohorts, respectively [57]
  1. Abbreviations: HGSOC high grade serious ovarian cancer, PFS progression free survival, OC ovarian cancer, CRPC castration resistant prostate cancer