| General information |
| Database: | DB00224 |
| Objective: | Tasquinimod (Active Biotech) is an oral immunomodulatory, antiangiogenic, and antimetastatic agent that delayed metastatic disease progression in a randomized placebocontrolledphase II trial in men with metastatic castrationresistant prostate cancer (mCRPC). Here, they report longterm survival with biomarker correlates from this trial. |
| Authors: | Armstrong AJ, et al |
| Title: | Longterm survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castrationresistant prostate cancer. |
| Journal: | Clin Cancer Res |
| Year: | 2013 |
| PMID: | 24255071 |
| Trial Design |
| Clinical Trial Id: | NCT00560482 |
| Agent: | tasquinimod
|
| Target: | Calgranulin B
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | minimally symptomatic metastatic castrateresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized placebocontrolledphase II trial |
| Key Patients Feature: | men with minimally symptomatic metastatic castrationresistant prostate cancer |
| Biomarker: | bone alkaline phosphatase and lactate dehydrogenase (LDH) and a transient induction of inflammatory biomarkers, VEGFA, and thrombospondin1 levels with tasquinimod. |
| Biomark Analysis: | Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGFA, and thrombospondin1 levels with tasquinimod. Baseline levels of thrombospondin1 less than the median were predictive of treatment benefit. |
| Control Group Info: | placebo |
| Treatment Info: | Fortyone men randomized to placebo crossed over to tasquinimod. |
| Primary End Point: | Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanismbased correlates with tasquinimod efficacy including progression free survival (PFS) and overall survival (OS). |
| Secondary End Point: | NA |
| Patients Number: | 201 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.350.78; P = 0.001] for PFS, favoring tasquinimod. |
| Median OS A vs. C: | With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively.median OS: 0.64 (95% CI, 0.420.97; P = 0.034) |
| Adverse Event(agent arm): | Toxicities tended to be mild in nature and improved over time. |
| Conclusions: | The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable riskbenefit ratio. |