| General information |
| Database: | DB00948 |
| Objective: | phase I trial of the 2drug regimen of everolimus plus gemcitabine (Cohort I) and the 3drug regimen of everolimus plus gemcitabine and cisplatin (Cohort II) was performed to determine the maximally tolerated dose (MTD) of both combinations. An expansion cohort (Cohort III) of patients with cholangiocarcinoma or gallbladder carcinoma was treated at the MTD. |
| Authors: | Costello BA, et al |
| Title: | Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors. |
| Journal: | Invest New Drugs. |
| Year: | 2014 |
| PMID: | 24740268 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | everolimus, gemcitabine + cisplatin |
| Study Type: | Phase I trial |
| Key Patients Feature: | To enroll in Cohort I or Cohort II, patients required histologic proof of malignancy that was unresectable and was not amenable to all standard treatment for the disease with the exception of cancers in which gemcitabine was considered an appropriate initial treatment option. For Cohort III, patients required histologic proof of advanced intrahepatic or extrahepatic cholangiocarcinoma, or gallbladder carcinoma. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | A standard 3 + 3 design dose escalation was used. Everolimus was given on Monday/theydnesday/Friday or daily depending upon the dose level. Gemcitabine and cisplatin were administered on days 1 and 8 of each 21 day cycle. |
| Primary End Point: | MTD, DLT and safety, CR, RR |
| Secondary End Point: | NA |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | The MTD for Cohort I was everolimus 5 mg on Monday/theydnesday/Friday and gemcitabine 800 mg/m(2). For Cohort II, it was everolimus 5 mg on Monday/theydnesday/Friday, gemcitabine 600 mg/m(2), and cisplatin 12.5 mg/m(2). All DLTs in this study were hematologic. |
| Objective Response Rate: | NA |
| 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): | NA |
| Conclusions: | This phase I clinical trial has demonstrated that these 2drug and 3drug combinations are generally well tolerated and safely administered. The main DLTs in both regimens they were hematologic, specifically thrombocytopenia. The 3drug combination can be considered as a platform for future studies in specific tumor types |