| General information |
| Database: | DB00526 |
| Objective: | The combination of lowdose radiotherapy with PARP inhibition has been shown to enhance antitumor efficacy through potentiating DNA damage. They combined lowdose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT888), a smallmolecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumor malignancies. |
| Authors: | Reiss KA, et al |
| Title: | a phase I study of veliparib (ABT888) in combination with lowdose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis. |
| Journal: | Clin Cancer Res. |
| Year: | 2015 |
| PMID: | 25355929 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | veliparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | veliparib (ABT888) + lowdose fractionated whole abdominal radiation therapy |
| Study Type: | multiinstitutionalphase I study |
| Key Patients Feature: | Eligible patients had an unresectable or metastatic solid tumor malignancy with the presenceof peritoneal carcinomatosis documented either via imaging, operative notes, clinical notesor symptoms. Measureable disease was not required as an eligibility criterion. Extraabdominal disease was permitted so long as peritoneal disease was dominant. Patients hadadequate organ function, an Eastern Cooperative Oncology Group (ECOG) performancestatus of less than and equal to 1 and a life expectancy of greater than 3 months |
| Biomarker: | Circulating tumor cells (CTC) were collected and evaluated for ¦ÃH2AX |
| Biomark Analysis: | An increased percentage of ¦ÃH2AXpositive CTCs was observed in a subset of patients (3/6 with >2 CTCs at baseline). |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with veliparib (80320 mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 13 of each cycle. Circulating tumor cells (CTC) were collected and evaluated for ¦ÃH2AX. Quality of life (QoL) was assessed using the EORTCQLQC30 questionnaire. |
| Primary End Point: | toxicity |
| Secondary End Point: | progression free survival (PFS), overall survival (OS) and quality of life, as evaluated bythe EORTCQLQC30 questionnaire. |
| Patients Number: | 22 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.47 months. In the subset of 8 ovarian and fallopian cancers (OV), mPFS was 6.77 months compared to mPFS 2.71 months in others. |
| Median OS A vs. C: | 13.04 months. In the subset of 8 ovarian and fallopian cancers (OV), mOS was 17.54 months compared to mOS 13.01 months in others. |
| Adverse Event(agent arm): | Treatmentrelated grade 3 and 4 toxicites included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%) and dyspnea (4%). No objective responses were observed. |
| Conclusions: | Combined veliparib and LDFWAR is a welltolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the ovarian and fallopian cancer subpopulation. |