| General information |
| Database: | DB00666 |
| Objective: | Preclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose findingphase I study the efficacy and toxicity of a fourdrug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (GemCap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer. |
| Authors: | Watkins DJ, et al |
| Title: | The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study. |
| Journal: | Eur J Cancer. |
| Year: | 2014 |
| PMID: | 24613126 |
| Trial Design |
| Clinical Trial Id: | NCT00260364 |
| Agent: | bevacizumab and erlotinib
|
| Target: | NA
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic ductal adenocarcinoma or undifferentiated carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | chemotherapy doublet (gemcitabine + capecitabine) with a biological doublet (bevacizumab + erlotinib) |
| Study Type: | an openlabel, singlecentrephase I/II study |
| Key Patients Feature: | Eligible patients were 18 years or older with histologically or cytologically proven locally advanced ormetastatic pancreatic ductal adenocarcinoma or undifferentiated carcinoma. patients were required to haveadequate renal, bone marrow and liver function (creatinine clearance P 50 mL/min, platelets > 100 109/L, leucocytes > 3.0 109/L, neutrophil count > 1.5 109/L and bilirubin < 2 the upper limit of normal), unidimensional measurable disease and have a WHO(World Health Organisation) performance status of62. No prior chemotherapy or radiotherapy wasallowed. Other key exclusion criteria included clinicallysignificant (i.e. active) cardiovascular disease, ongoingtreatment with aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration, central nervous system metastases, uncontrolledhypertension, major surgery/traumatic injury within28 days, nonhealing wound/fracture, major bleedingdiathesis or fulldose anticoagulation and uncontrolledcomorbid conditions. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received gemcitabine (1000mg/m(2) D1, 8, 15), capecitabine (1400mg/m(2) D121), erlotinib (100mg daily) and bevacizumab (5mg/kg D1, 15) every 28 days. Computed tomography (CT) assessment was performed every 8weeks. Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment. |
| Primary End Point: | radiological response rate |
| Secondary End Point: | NA |
| Patients Number: | 44 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Confirmed radiological responses were seen in 23% (95% confidence interval (CI): 1138%) of patients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.4 months |
| Median OS A vs. C: | 12.6 months. In patients with metastatic disease the median overall survival was 10.1 months. |
| Adverse Event(agent arm): | Common grade 3/4 toxicities were; neutropenia 52%, lethargy 32%, diarrhoea 18% and handfoot syndrome 18%. |
| Conclusions: | The combination of gemcitabine, capecitabine, erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population. |