Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma
The purpose of this study is to estimate the time to disease progression when everolimus and pasireotide are given together in patients with advanced or metastatic HCC who have not had any prior systemic therapy.
Advanced Adult Hepatocellular Carcinoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Single Arm Study of Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC)|
- Time to Progression (TTP) [ Time Frame: 7 years ] [ Designated as safety issue: No ]Time to progression is defined as the time from study enrollment until radiological progression in a previously embolized lobe, development of new lesions in an untreated lobe, or evidence of extrahepatic progression (based on modified HCC RECIST criteria). Patients will be followed until death. Patients that die of causes unrelated to the study drug without evidence of progression will be censored.
- Number of Individuals Experiencing Toxicity [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]Safety determinations are based on the rate of drug-related AEs reported based upon the toxicity as measured by the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
- Overall survival (OS) [ Time Frame: 7 years ] [ Designated as safety issue: No ]Overall survival is defined as the time from study enrollment until death.
- Objective Response Rate (ORR) [ Time Frame: 7 years ] [ Designated as safety issue: No ]Objective response rate (ORR) is defined as the rate of complete responses (CRs) + partial responses (PRs) as determined by RECIST and modified HCC RECIST criteria.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Everolimus + pasireotide
Oral Everolimus 7.5 mg administered daily for 28 days per cycle, plus pasireotide LAR 60 mg administered by intramuscular injection once per 28 day cycle on day 1.
Everolimus 7.5 mg administered daily for 28 days per cycle until disease progression or unacceptable toxicity.
Other Names:Drug: Pasireotide
Monthly (every 28 days) intramuscular injection of long-acting pasireotide (pasireotide LAR 60 mg) repeated on day 1 of every 28 day cycle until disease progression or unacceptable toxicity.
This open label, single-arm Phase II study will assess time to progression (TTP) and safety of everolimus and pasireotide in patients with advanced or metastatic hepatocellular carcinoma (HCC) and limited prior systemic therapy. Should this regimen demonstrate efficacy, this will support a Phase III randomized clinical trial of this combination therapy. At least 30 patients will be enrolled into this Phase II study. Additionally, given the potential importance of the RAS/RAF/MEK/ERK and RAS/pAKT pathways, we propose to correlate outcomes with baseline pAKT, p-S6, somatostatin receptor tumor expression, and serum VEGF expression. We anticipate these exploratory analyses will increase understanding of the molecular pathways and their inhibition in this disease. The study will be performed as a University of North Carolina-coordinated, multicenter study.
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, North Carolina|
|University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|Comprehensive Cancer Center of Wake Forest University|
|Winston-Salem, North Carolina, United States, 27157|
|Principal Investigator:||Bert H O'Neil, MD||University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center|