| General information |
| Database: | DB00790 |
| Objective: | Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and etoposide (E) in preclinical models of SCLC. they conducted thisphase 1 study to establish the safety of the combination in human subjects. |
| Authors: | Owonikoko TK, et al |
| Title: | a phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOGACRIN Cancer Research Group (E2511). |
| Journal: | Lung Cancer. |
| Year: | 2015 |
| PMID: | 25985977 |
| Trial Design |
| Clinical Trial Id: | NCT01642251 |
| Agent: | veliparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | smallcell lung cancer |
| Cancer Subtype: | extensive stage small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | veliparib combined with cisplatin + etoposide |
| Study Type: | a phase I safety study |
| Key Patients Feature: | Patients with treatmentna ve, extensive stage SCLC were included. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The study employed the 3+3 dose escalation design to establish the safety and recommendedphase 2 dose (RP2D) of V when combined with fixed doses of C (75 mg/m(2) on day 1) and E (100mg/m(2) on days 13) in a 21day cycle. The starting dose of V was 60 mg (bid days 17) with plan to escalate to 100mg (days 17) or deescalate to 40 mg (days 17) depending on the dose limiting toxicity (DLT) experience during cycle 1. |
| Primary End Point: | safety and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 9 |
| Trial Results |
| DLT_MTD: | The starting dose of veliparib was 60 mg with plan to either escalate to the higher dose level of 100 mg if dose limiting toxicity (DLT) in <33% of patients or to deescalate to 40 mg dose if DLT was observed in more than and equal to 33% of treated patients. DLT was defined during the first cycle only and the following toxicities, graded according to the standardized NCI CTCAE version 4.0 criteria constituted DLT on the study: grade 4 thrombocytopenia, grade 4 anemia, grade 4 neutropenia, grade 3 neutropenia with persistent fever (febrile neutropenia) for more than 7 days, grade 4 fever and neutropenia (febrile neutropenia) of any duration and grade more than and equal to 3 nonhematologic toxicity of any duration that is not an expected toxicity of CE regimen (excluding alopecia, lab values that did not warrant clinical intervention and any grade more than and equal to 3 electrolyte abnormality that resolved within 24 h). |
| Objective Response Rate: | 71.40% |
| Disease Control Rate: | 100% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 9.0 months (95% CI: 4.8-not reached). |
| Adverse Event(agent arm): | NA |
| Conclusions: | This study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients |