Entry Detail
| General information | |
| Database: | DB00670 |
| Objective: | Chemotherapy has yielded minimal clinical benefit in pancreatic and biliary tract cancer. A highdose, short course capecitabine schedule with oxaliplatin, has shown some efficacy with a lotheyr incidence of palmarplantar erythrodysesthesia. Achieving high exposures of the targeted agent sorafenib may be possible with this shorter schedule of capecitabine by avoiding dermatologic toxicity. |
| Authors: | LoConte NK, et al |
| Title: | a phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 23263993 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | pancreatic and biliary tract cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | sorafenib, oxaliplatin and 2 days of high dose capecitabine |
| Study Type: | an open label, multicenterphaseI/II trial |
| Key Patients Feature: | have histologically or cytologically confirmedadenocarcinoma of the pancreas or biliary tract withoutmore than one prior systemic treatment for his or her disease. Eligible patients were required to have at least onemeasurable lesion as defined by RECISTv1.0 [26]. Allparticipating patients had to be at least 18 years of age, havean Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and have adequate organ and marrowfunction (including leukocytesmore than and equal to 3, 000/¦Ìl, absolute neutrophil count more than and equal to 1, 500/¦Ìl, platelets more than and equal to 100, 000/¦Ìl, total bilirubinless than and equal to 2.5 x institutional upper limit of normal (ULN), AST(SGOT)/ALT (SGPT)less than and equal to 5 X ULN, creatinine clearancemore than and equal to 50 mL/min as calculated by the CockcroftGault formula). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Cohort 1 used sorafenib 200 mg BID, and cohort 2 used sorafenib 400 mg BID. |
| Treatment Info: | Patients in both cohorts received oxaliplatin 85 mg/m2 followed by capecitabine 2, 250 mg/m2 PO every 8 h x 6 doses starting on days 1 and 15 of a 28 day cycle, or 2DOC (2 Day Oxaliplatin/Capecitabine). Cohort 1 used sorafenib 200 mg BID, and cohort 2 used sorafenib 400 mg BID. |
| Primary End Point: | MTD, DLT and toxicities. |
| Secondary End Point: | NA |
| Patients Number: | 16 |
| Trial Results | |
| DLT_MTD: | Cohort 1 used sorafenib 200 mg BID, which represented the MTD. |
| Objective Response Rate: | Two partial responses were seen, one each in pancreatic and biliary tract cancers. The recommendedphase II dose of sorafenib in combination with 2DOC is 200 mg BID. |
| 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): | Across all cycles the most common grade 1 or 2 adverse events were fatigue (10 pts), diarrhea (10 pts), nausea (9 pts), vomiting (8 pts), sensory neuropathy (8 pts), thrombocytopenia (7 pts), neutropenia (5 pts), and handfoot syndrome (5 pts). Grade 3 toxicites included neutropenia, mucositis, fatigue, vomiting and diarrhea. |
| Conclusions: | The recommendedphase II dose of sorafenib in combination with 2DOC is 2 |