Entry Detail
| General information | |
| Database: | DB00231 |
| Objective: | Thisphase I doseescalation study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics (PDs), and preliminary antitumor activity of BGT226, a potent, oral dual phosphatidylinositol3kinase (PI3K)/mammalian target of rapamycin inhibitor. |
| Authors: | Markman B, et al |
| Title: | Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol3kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors. |
| Journal: | Ann Oncol |
| Year: | 2012 |
| PMID: | 22357447 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | BGT226 |
| Target: | PI3K gamma Serine/threonineprotein kinase mTOR |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I doseescalation study |
| Key Patients Feature: | patients with advanced solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients with advanced solid tumors received BGT226 2.5125 mg/day three times weekly (TIW). Dose escalation was guided by an adaptive Bayesian logistic regression model with overdose control. |
| Primary End Point: | response per RECIST, [18F]fluorodeoxyglucose uptake, and phosphorylatedS6 in skin and paired tumor samples. |
| Secondary End Point: | NA |
| Patients Number: | 57 |
| Trial Results | |
| DLT_MTD: | Three patients (125 mg cohort) had doselimiting toxic effects (grade 3 nausea/vomiting, diarrhea).The MTD of BGT226 was 125 mg/day TIW, and the clinically recommended dose was 100 mg/day TIW. |
| Objective Response Rate: | Seventeen patients (30%) had stable disease (SD) as best response. Nine patients had SD for more than and equal to 16 weeks. Thirty patients (53%) achieved stable metabolic disease as assessed by [18F]fluorodeoxyglucosepositron emission tomography; however, no correlation between metabolic response and tumor shrinkage according to computed tomography was observed. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | The MTD of BGT226 was 125 mgday TIW, and the clinically recommended dose was 100 mgday TIW. Limited preliminary antitumor activity and inconsistent target inhibition were observed, potentially due to low systemic exposure. |