Entry Detail
| General information | |
| Database: | DB00161 |
| Objective: | Resistance to chemotherapyinduced apoptosis represents a major obstacle to cancer control. Overexpression of Bcl2 is seen in multiple tumor types and targeting Bcl2 may provide therapeutic benefit. a phase I study of navitoclax, a novel inhibitor of Bcl2 family proteins, was conducted to evaluate safety, pharmacokinetics, and preliminary efficacy in patients with solid tumors. |
| Authors: | Gandhi L, et al |
| Title: | Phase I study of Navitoclax (ABT263), a novel Bcl2 family inhibitor, in patients with smallcell lung cancer and other solid tumors. |
| Journal: | J Clin Oncol |
| Year: | 2011 |
| PMID: | 21282543 |
| Trial Design | |
| Clinical Trial Id: | NCT00445198 |
| Agent: | navitoclax |
| Target: | Bcl2like protein 2 Antiapoptotic protein BCLXL Apoptosis regulator Bcl2 |
| 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: | in patients with relapsed or refractory SCLC and other solid tumors. |
| Biomarker: | Progastrin releasing peptide (proGRP) was identified as a surrogate marker of Bcl2 amplification and changes correlated with changes in tumor volume. |
| Biomark Analysis: | Progastrin releasing peptide (proGRP) was identified as a surrogate marker of Bcl2 amplification and changes correlated with changes in tumor volume. |
| Control Group Info: | single arm |
| Treatment Info: | Patients enrolled to intermittent dosing cohorts received navitoclax on day 3, follotheyd by dosing on days 1 to 14 of a 21day cycle. Patients on continuous dosing received a 1week leadin dose of 150 mg follotheyd by continuous daily administration. |
| Primary End Point: | safety (with particular attention to platelet dynamics), pharmacokinetics, and preliminary efficacy |
| Secondary End Point: | NA |
| Patients Number: | 47 |
| Trial Results | |
| DLT_MTD: | A leadin dose of 150 mg was chosen, as this was the dose level at which the mean maximal platelet drop of approximately 60% from baseline was expected based on observations in other concurrent studies of navitoclax as a single agent. |
| Objective Response Rate: | NA |
| Disease Control Rate: | One patient with SCLC had a confirmed partial response lasting longer than 2 years, and eight patients with SCLC or carcinoid had stable disease (one remained on study for 13 months). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Primary toxicities included diarrhea (40%), nausea (34%), vomiting (36%), and fatigue (34%); most were grade 1 or 2. Dose and scheduledependent thrombocytopenia was seen in all patients. |
| Conclusions: | Navitoclax is safe and well tolerated, with dosedependent thrombocytopenia as the major adverse effect. Preliminary efficacy data are encouraging in SCLC. Efficacy in SCLC and the utility of proGRP as a marker of treatment response will be further evaluated inphase II studies |