| General information |
| Database: | DB00849 |
| Objective: | Phosphatidylinositol3kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxanebased chemotherapy. Thisphase I study combines buparlisib, a panclass 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452). |
| Authors: | Hyman DM, et al |
| Title: | Parallelphase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors. |
| Journal: | Cancer Chemother Pharmacol. |
| Year: | 2015 |
| PMID: | 25672916 |
| Trial Design |
| Clinical Trial Id: | NCT01297452 |
| Agent: | buparlisib
|
| Target: | PI3K delta, PI3K gamma, PI3K beta, PI3K alpha
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | buparlisib (BKM120) + carboplatin + paclitaxel |
| Study Type: | Parallelphase Ib studies |
| Key Patients Feature: | patients with advanced solid tumors;Eligible patients had received no more than two prior cytotoxic chemotherapy regimens for recurrent and/or metastatic disease. Laboratory evidence of adequate function of bone marrow, liver, and kidneys was required |
| Biomarker: | loss of PTEN expression |
| Biomark Analysis: | Among three patients with known loss of PTEN expression, all derived clinical benefit from treatment. |
| Control Group Info: | single arm |
| Treatment Info: | There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m(2), on day 1 of a 21day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m(2) (days 1, 8, and 15) on a 28day cycle without growth factor support. In both groups, three dose levels of buparlisib were explored: 50, 80, and 100 mg/day |
| Primary End Point: | Primary endpoint was to identify recommendedphase II doses of buparlisib in both groups. |
| Secondary End Point: | NA |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | The DLTs were elevated alkaline phosphatase (n = 1) and uncomplicated neutropenia (n = 2).The DLTs were elevated alkaline phosphatase (n = 1) and uncomplicated neutropenia (n = 2). |
| Objective Response Rate: | 20% |
| 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): | Because it is not possible to exclude fully a role for buparlisib in potentially intensifying toxicities of carboplatin and paclitaxel, adverse events are provided regardless of the investigators¡¯ attributions of causality. Hyperglycemia, as expected, was common in both groups. |
| Conclusions: | The addition of buparlisib to carboplatin + paclitaxel was well tolerated, and preliminary activity was notable against tumors with loss of PTEN expression. |