| General information |
| Database: | DB00151 |
| Objective: | Randomized, phase I, and pharmacokinetic (PK) study of RAD001, an mTOR inhibitor, in patients (pts) with advanced hepatocellular carcinoma (hepatocellular carcinoma). The study aims to define the doselimiting toxicity (DLT), maximum tolerated dose (MTD) and PK of daily and weeklydosing RAD001 in advanced hepatocellular carcinoma pts. |
| Authors: | L. Chen, et al |
| Title: | Randomized, phase I, and pharmacokinetic (PK) study of RAD001, an mTOR inhibitor, in patients (pts) with advanced hepatocellular carcinoma (hepatocellular carcinoma). |
| Journal: | J Clin Oncol |
| Year: | 2009 ASCO Annual Meeting |
| PMID: | J Clin Oncol 27:15s, 2009 (suppl; abstr 4587) |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma not amenable to surgical or regional therapies |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Randomized, phase I, and pharmacokinetic (PK) study |
| Key Patients Feature: | Advanced hepatocellular carcinoma pts who were not feasible for or progressed after local therapy (surgery, percutaneous ablation or transcatheter arterial chemoembolization), ECOG PS 02, ChildPugh's score < 8, and adequate hepatic, renal and hematological functions were eligible(M/F 34/2; median age 58.5, range 2875; ChildPugh's class of A/B 31/5) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The doses of RAD001 for dailydosing arm would be escalated from 2.5, 5.0, 7.5 to 10.0 mg, and from 20, 30, 50 to 70 mg in weeklydosing arm. Four weeks of treatment was regarded as one cycle. PK samples were collected on days 1 of cycle 1 and 2. |
| Primary End Point: | doselimiting toxicity (DLT), maximum tolerated dose (MTD) and PK |
| Secondary End Point: | NA |
| Patients Number: | 36 |
| Trial Results |
| DLT_MTD: | Number of pts with DLT/enrollment for dose level I, II, III and IV in daily arm was 1/6 (grade 3 hyperbilirubinemia), 1/6 (grade 4 thrombocytopenia), 0/3 and 2/3 (grade 3 diarrhea and rectal bleeding in 1 and grade 3 diarrhea and cardiac ischemia in 1), respectively; whiles in weekly arm was 0/3, 1/6 (grade 3 ALT elevation), 0/3 and 1/6 (grade 3 infection), respectively. MTD for weekly and daily dosing schedule was 70 mg and <7.5 mg, respectively. |
| Objective Response Rate: | NA |
| Disease Control Rate: | The disease control response (DCR) of 31 evaluable pts was 61% (10/16) and 46.7% (7/15, including one PR) of pts receiving daily and weekly treatment, respectively. however, the DCR for weeklydosing pts received >50 mg was 75% (4/6). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Patient accrual is ongoing to complete. Hotheyver, preliminary data suggest RAD001 is moderately active in stabilizing the progression of hepatocellular carcinoma, and PK data will be important to determine the optimal dosing schedule of RAD001 for hepatocellular carcinoma pts. |