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Clinical Trial
. 2019 Jan 1;25(1):73-79.
doi: 10.1158/1078-0432.CCR-18-0110. Epub 2018 Aug 21.

Phase II Study of Iniparib with Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma

Jaishri O Blakeley  1   2 , Stuart A Grossman  2 , Andrew S Chi  3 , Tom Mikkelsen  4 , Myrna R Rosenfeld  5 , Manmeet S Ahluwalia  6 , L Burt Nabors  7 , April Eichler  8 , Ignacio Garcia Ribas  9 , Serena Desideri  10 , Xiaobu Ye  2 ; Adult Brain Tumor Consortium
Affiliations
Clinical Trial

Phase II Study of Iniparib with Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma

Jaishri O Blakeley et al. Clin Cancer Res. .

Abstract

Purpose: Iniparib is a purported prodrug causing cell death through intracellular conversion to nitro radical ions. We assessed the efficacy and safety of iniparib with standard radiotherapy and temozolomide in patients with newly diagnosed glioblastoma (GBM).

Patients and methods: Adults meeting eligibility criteria were enrolled in this prospective, single-arm, open-label multi- institution phase II trial with median overall survival (mOS) compared with a historical control as the primary objective. A safety run-in component of radiotherapy + temozolomide + iniparib (n = 5) was followed by an efficacy study (n = 76) with the recommended phase II doses of iniparib (8.0 mg/kg i.v. twice/week with radiotherapy + daily temozolomide followed by 8.6 mg/kg i.v. twice/week with 5/28-day temozolomide).

Results: The median age of the 81 evaluable participants was 58 years (63% male). Baseline KPS was ≥ 80% in 87% of participants. The mOS was 22 months [95% confidence interval (CI), 17-24] and the HR was 0.44 (95% CI, 0.35-0.55) per-person-year of follow-up. The 2- and 3-year survival rates were 38% and 25%, respectively. Treatment-related grade 3 adverse events (AEs) occurred in 27% of patients; 9 patients had AEs requiring drug discontinuation including infusion-related reaction, rash, gastritis, increased liver enzymes, and thrombocytopenia.

Conclusions: Iniparib is well tolerated with radiotherapy and temozolomide in patients with newly diagnosed GBM at up to 17.2 mg/kg weekly. The primary objective of improved mOS compared with a historical control was met, indicating potential antitumor activity of iniparib in this setting. Dosing optimization (frequency and sequence) is needed prior to additional efficacy studies.

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Conflict of interest statement

Conflict of Interest: The authors JOB, SAG, AC, TM, MRR, MSA, LBN, AE, SD, XY declare no potential conflicts of interest. IGR was an employee of Sanofi at the time of the design and launch of the study.

Figures

Figure 1.
Figure 1.
Study schema for the safety run-in and efficacy study. Intention to treat analysis included all patients treated at the target dose (total N=81). RT = radiation therapy; Gy = gray; TMZ = temozolomide; IV = intravenous; DLT = dose limiting toxicity; MRI = magnetic resonance imaging.
Figure 2.
Figure 2.
mOS with 95% CI for all patients in the intention to treat analysis. The dot and line correspond to the mOS with 95% CI from EORTC/NCIC (1).
See this image and copyright information in PMC

References

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