| General information |
| Database: | DB00159 |
| Objective: | they conducted a phase I trial of the PARP inhibitor veliparib and metronomic cyclophosphamide in patients with refractory solid tumors and lymphoid malignancies. |
| Authors: | Kummar S, et al |
| Title: | a phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22307137 |
| Trial Design |
| Clinical Trial Id: | NCT00810966 |
| Agent: | veliparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | refractory solid tumors and lymphoid malignancies |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | veliparib + metronomic cyclophosphamide |
| Study Type: | an openlabel, multicenter, singlearmphase I combination study |
| Key Patients Feature: | Patients (age more than and equal to 18 years) were eligible if they had pathologically confirmed metastatic solid tumor or lowgrade lymphoma for which there was no acceptable standard therapy |
| Biomarker: | DNAdamage marker ¦ÃH2AX in PBMCs and circulating tumor cells (CTC). |
| Biomark Analysis: | ¦ÃH2AX levels were increased in CTCs from seven of nine patients evaluated after drug administration |
| Control Group Info: | single arm |
| Treatment Info: | Cyclophosphamide was administered once daily in 21day cycles in combination with veliparib administered once daily for 7, 14, or 21 days. |
| Primary End Point: | safety and maximum tolerated dose (MTD) of the combination; characterize veliparib pharmacokinetics (PK);poly(ADPribose) (PAR), in tumor biopsies and peripheral blood mononuclear cells (PBMC); and measure the DNAdamage marker ¦ÃH2AX in PBMCs and circulating tumor cells (CTC). |
| Secondary End Point: | NA |
| Patients Number: | 35 |
| Trial Results |
| DLT_MTD: | The study treatment was well tolerated, and the MTD was established as veliparib 60 mg with cyclophosphamide 50 mg given once daily. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Seven patients had partial responses; an additional six patients had disease stabilization for at least six cycles. PAR was significantly decreased in PBMCs (by at least 50%) and tumor biopsies (by at least 80%) across dose levels (DL); ¦ÃH2AX levels were increased in CTCs from seven of nine patients evaluated after drug administration. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | The combination of veliparib with metronomic cyclophosphamide is well tolerated and shows promising activity in a subset of patients with BRCA mutations. Aphase II trial of the combination compared with singleagent cyclophosphamide is ongoing in BRCApositive ovarian cancer, triplenegative breast cancer, and lowgrade lymphoma. |