Background: Setting appropriate efficacy endpoint(s) in Phase II clinical trials is important for success in subsequent Phase III trials or for conditional approval based on Phase II findings. However, there is no consensus about efficacy endpoints in Phase II trials targeting glioblastoma.
Objective: To compare endpoints used in recent Phase II clinical trials of glioblastoma treatments.
Method: 117 clinical trials involving glioblastoma were identified on the ClinicalTrials.gov website. The main efficacy endpoints used in them were examined.
Results: Seventeen trials had no efficacy endpoint and were excluded. Efficacy endpoints in the remaining 100 trials were OS in 33 trials (29%), response rate in 23 (20%), PFS in 20 (17%), OS rate in 11 (10%), PFS rate in 10 (9%), and others in 16 (14%) (note that multiple endpoints were used in some trials). Response rates ranged from 2 cases of 45 (4%) for newly diagnosed glioblastoma to 20 of 51 (39%) for recurrent glioblastoma (p = 0.0004). Response rate evaluation was done using RANO criteria in 9 trials, iRANO in 2 trials, RECIST in 2 trials, and unknown in 9 trials. In 20 trials that employed OS rate or PFS rate as an efficacy endpoint, the timing of the efficacy evaluation was 12.0 months (median value) [range: 12.0 to 12.0 months] for OS and 6.0 [6.0 to 12.0] months for PFS in cases of newly diagnosed glioblastoma, and 12.0 [6.0 to 24.0] months for OS and 6.0 [6.0 to 12.0] months for PFS in recurrent glioblastoma. The timing of efficacy evaluation appears to be earlier than the median in pivotal studies of previously approved products.
Conclusions: Various efficacy endpoints have been set in Phase II clinical trials targeting glioblastoma, and there is no consensus as to which endpoint should be preferred. In trials using time-to-event endpoints, some of the study designs make it difficult to interpret the results.

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Quantitative methods for determining magnolol, [6]-gingerol, and rosmarinic acid in Hangekobokuto Extract are specified in the Japanese Pharmacopoeia 17th edition (JP17). Standard substances of these measurement components are used in the quantitative methods, but it is difficult to ensure consistent quality of these standards.
In this study, therefore, we aimed to establish a quantitative method not requiring the use of standard target substances. For this purpose, we investigated an analytical method to simultaneously quantify magnolol, [6]-gingerol, and rosmarinic acid in Hangekobokuto Extract by using 4-hydroxybenzoic acid propyl ester as a standard, based on the mass absorption coefficient ratios, determined by dividing the absorbance ratio measured by HPLC by the mass ratio corrected for purity.
The results obtained with this method agreed with those determined using the quantitative methods specified by JP17 within a 3% tolerance. Thus, evaluation based on the ratio of mass absorption coefficients with respect to 4-hydroxybenzoic acid propyl ester as an alternative standard appears to be a useful method for the quantitation of magnolol, [6]-gingerol, and rosmarinic acid in Hangekobokuto Extract. A similar approach might also be applicable to other components of other extracts.

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In this study, we evaluated how different types of membrane or illumination method could affect the measurement result of the Membrane Microscope method in the JP <6.07> Insoluble Particulate Matter Test for Injections. Our study reveals the points to consider in the determination of protein particles by using Membrane Microscope methods.

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