Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.
- Conditions
- Carcinoma
- Interventions
- Registration Number
- NCT01035229
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study is to compare treatment with RAD001 plus best supportive care (BSC) to placebo plus BSC in patients with advanced HCC whose disease progressed while on or after sorafenib treatment or who are intolerant to sorafenib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 546
-
Advanced liver cancer
-
Prior systemic treatment with sorafenib for advanced HCC and for whom their disease progressed during or after sorafenib treatment, or were intolerant to sorafenib treatment. Specifically, this can be defined as:
- Documented radiological confirmation (radiology scans or report) of disease progression during or after sorafenib treatment
- Intolerance to sorafenib (at any dose and/or duration) is defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation.
NOTE:
-
Sorafenib must be the last antineoplastic treatment before randomization
-
Prior local and/or hormonal therapy (e.g., tamoxifen) before sorafenib is allowed
-
One systemic chemotherapy regimen for advanced HCC is allowed before sorafenib treatment
- ECOG performance status of ≤ 2
- Child-Pugh A
- Active bleeding during the last 28 days
- Prior therapy with mTOR inhibitors
- Prior liver or other organ transplantation which mandates systemic immunosuppression
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Best Supportive Care Everolimus Placebo Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice. Everolimus + Best Supportice Care (BSC) Best Supportive Care (BSC) Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice. Everolimus + Best Supportice Care (BSC) Everolimus Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice. Placebo + Best Supportive Care Best Supportive Care (BSC) Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) When 454 OS events were observed OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.
- Secondary Outcome Measures
Name Time Method Time to Tumor Progression (TTP) Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient TTP was defined as the time from the date of randomization to the date of the first documented radiologic confirmation of disease progression. Since the study did not meet the primary objective, TTP was not formally tested.
Percentage of Participants With Disease Control Rate (DCR) Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient DCR is defined as the proportion of participants with a best objective response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST. The BOR was the best response recorded from the start of the treatment until disease progression. CR is disappearance of all target lesions; PR is at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is at least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
Time to Definitive Deterioration of ECOG Performance Score (PS) Score Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient. Change in Eastern Cooperative Oncology Group (ECOG) were assessed by time to definitive performance status deterioration by at least one category on the ECOG scale. Deterioration was considered definitive if no improvement in the ECOG PS was observed at a subsequent measurement. ECOG PS: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5=Dead
Time to Definitive Deterioration of EORTC QLQ-C30 Scores Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient. The primary quality of life endpoint was the time to definitive 5% deterioration from baseline in the global health status/quality of life scale of the EORTC QLQ-C30 questionnaire. Definitive deterioration by at least 5% is defined as a decrease in score by at least 5% compared to baseline, with no later observed increase above this threshold. The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the healthrelated quality of life (QoL) of cancer patients participating in international clinical trials. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Pharmacokinetics Assessments - Cmin Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient. Cmin is the pre-dose blood concentration at steady-state (ng/mL). Pre-dose (Cmin) blood samples were collected from all patients in both arms at Visit 3. Steady-state for the Cmin sample was defined as continuous administration of the same dose in the last 4 days prior to the collection of the Cmin sample. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid pre-dose (Cmin) everolimus samples were included in the analysis.
Pharmacokinetics Assessments - Cmax Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient. Cmax is the maximum (peak) blood drug concentration after dose administration (ng/mL) calculated as the maximum of C1h and C2h. C1h was 1 hour post-dose blood concentration (ng/mL) and C2h was 2 hour post-dose blood concentration (ng/mL). C1h and C2h post-dose samples were collected from all patients in both arms at Visit 3. Steady-state for the C1h and C2h samples was defined as continuous administration of the same dose in the previous 4 days and the day on which the C1h and C2h samples were collected. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid C1h and C2h everolimus samples were included in the analysis.
Trial Locations
- Locations (20)
Novartis Investigative Site
🇹🇭Bangkok, Thailand
University of California San Diego - Moores Cancer Center SC - 3
🇺🇸La Jolla, California, United States
Compassionate Cancer Care Medical Group CCCMG
🇺🇸Fountain Valley, California, United States
California Pacific Medical Center California Pacific Med
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers RMCC - Denver-Midtown (4)
🇺🇸Greenwood Village, Colorado, United States
The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Dept. of SKCC @ JHU
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital Dept. of Mass General Hospital
🇺🇸Boston, Massachusetts, United States
Midwest Cancer Care Physicians Research Medical Center
🇺🇸Kansas City, Missouri, United States
VA Sierra Nevada Health Care System Dept. of VA Sierra Nevada HCS
🇺🇸Reno, Nevada, United States
Northwest Cancer Specialists Rose Quarter Cancer Center
🇺🇸Portland, Oregon, United States
St. Luke's Hospital and Health Network St. Luke's Cancer Network (2)
🇺🇸Bethlehem, Pennsylvania, United States
Methodist Charlton Cancer Center Methodist
🇺🇸Dallas, Texas, United States
Texas Cancer Center - Abilene
🇺🇸Abilene, Texas, United States
University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(3)
🇺🇸Dallas, Texas, United States
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
🇺🇸San Antonio, Texas, United States
Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Queen's Medical Center Queens Cancer Center
🇺🇸Honolulu, Hawaii, United States
University of Washington Cancer Care SC
🇺🇸Seattle, Washington, United States
University of Rochester Medical Center Rochester
🇺🇸Rochester, New York, United States
Highlands Oncology Group Dept of Highlands Oncology Grp
🇺🇸Fayetteville, Arkansas, United States