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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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25 November 2019 |
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Main ID: |
EUCTR2008-004096-21-NL |
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Date of registration:
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24/09/2008 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A phase 1 open label/phase 2 randomized, double-blind, multicenter study investigating the combination of RAD001 and sorafenib (Nexavar®) in patients with advanced hepatocellular carcinoma - NA
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Scientific title:
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A phase 1 open label/phase 2 randomized, double-blind, multicenter study investigating the combination of RAD001 and sorafenib (Nexavar®) in patients with advanced hepatocellular carcinoma - NA |
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Date of first enrolment:
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23/12/2008 |
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Target sample size:
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130 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004096-21 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: no
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over:
Other: yes
Other trial design description: phase 1: open, non-randomized; phase 2: double-blind, randomized
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
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Phase:
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Human pharmacology (Phase I): yes
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Germany
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Netherlands
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
1. Male or female patients = 18 years old with ability to take oral drugs
2. Diagnosis of advanced HCC according to the AASLD Guidelines (Bruix and Sherman 2005)
3. HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC) (Llovet, et al 2008b)
4. No previous systemic therapy for HCC, (tamoxifen is allowed as previous systemic therapy)
5. Measurable disease according to RECIST, i.e. at least one measurable lesion. This lesion should not have been previously treated with local therapy. A treated lesion may be used where these lesions are the only lesions available for evaluation and have shown definite progression since their last local radiation treatment. Local therapy must have been completed at least four weeks prior to baseline evaluation
6. Patients with ECOG performance status of 0 or 1 (see Section 7.5.4)
7. Cirrhotic status of current Child-Pugh class A only (5-6 points) with no encephalopathy and no ascites (ascites controlled by diuretics is excluded). Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
8. For patients with background chronic hepatitis B virus (HBV), they must be treated with lamivudine QD 100 mg, (or alternative treatment if resistant to lamivudine), as prophylaxis at least 2 weeks prior to receiving study drug, Visit 2.
9. The following laboratory parameters at Visit 2:
• Absolute Neutrophil Count (ANC) = 1.5 x 109/L
• Platelets = 70000 x 106/L
• Hemoglobin (Hgb) = 9 g/dL
• Serum aspartate aminotransferase (AST) and alanine amino-transferase (ALT) = 5 x ULN
• Serum creatinine = 1.5 x ULN
10. Ability to understand and willingness to sign a written informed consent and to be able to follow the visit schedule
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
1. Patients currently receiving any anti cancer therapy or who have received any local anti cancer therapy = 4 weeks prior to baseline CT/MRI scan, Visit 2
2. Active bleeding during the last 30 days prior to Visit 1 including variceal bleeding (Esophageal varices should be treated according to standard practice e.g. ligation/banding and procedure completed 30 days prior to Visit 1.)
3. Patients with a known hypersensitivity to RAD001 (everolimus) or known hypersensitivity to sorafenib or contradictions to sorafenib based on the local sorafenib label
4. Known previous/current malignancy requiring treatment within = 3 years except for cervical carcinoma in situ, basal cell carcinoma, and superficial bladder carcinoma 5. Known history of human immunodeficiency virus (HIV) seropositivity, (HIV testing is not mandatory)
6. Any severe and/or uncontrolled medical conditions including:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months prior to Visit 1, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
• Previous TIA, CVA, symptomatic PVD within last 6 months of Visit 1
• Patients with active alcohol intake
• Uncontrolled diabetes as defined by HbA1c >8%
• Greater or equal grade 3 hypercholesterolemia/hypertriglyceridemia or = grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given)
• Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy, in the opinion of the investigator, except chronic HBV or hepatitis C virus (HCV).
• Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
• Significant deterioration of lung function, defined as any of the following: 30% decrease in predicted lung volumes, and/or 30% decrease in DLCO, and/or = 88% O2 saturation at rest on room air
7. Patients receiving chronic treatment with corticosteroids (except for intermittent topical or
local injection or aldosterone) or another immunosuppressive agent
8. Patients treated with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A (see Table 6-5) unless the drugs are medically necessary and no substitutes are available. If there are no acceptable substitutes, special precautions should be taken in these patients (see Section 6.5.8.8).
9. Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from surgery
10. Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. Adequate contraceptives must be used throughout the trial and for 3 months after last study drug administration in both sexes. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of RAD001 and/or sorafenib.
11. Patients who have received an investigative drug or therapy
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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advanced hepatocellular carcinoma
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Intervention(s)
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Product Name: RAD001
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351696
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Product Name: RAD001
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351696
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Trade Name: Nexavar 200 mg film-coated tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sorafenib
CAS Number: 284461-73-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
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Primary Outcome(s)
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Primary end point(s): Phase 1
• Probability of DLT (Dose Limiting Toxicity) occurring during the first 28
days of combined treatment of RAD001 with sorafenib
Phase 2
• Time to Progression
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Main Objective: This is a combined phase 1 and phase 2 study with the following primary objectives:
Phase 1
• safety and tolerability of daily RAD001 in combination with daily sorafenib in adult patients with advanced hepatocellular carcinoma (HCC) who have taken no prior systemic therapy for HC and to determine the maximum tolerated dose (MTD) of the combination of RAD001 plus sorafenib to bring forward into phase 2
Phase 2
• To estimate the hazard ratio of the treatment effect as a measure of anti-tumor activity in terms of Time to Progression (TTP) of the combination of RAD001 plus sorafenib, at the MTD level, as compared to sorafenib alone
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Secondary Objective: Phase 1
• efficacy of RAD001 + sorafenib at the explored dose-levels in terms of best overall response as defined by RECIST
• safety and tolerability of of RAD001 + sorafenib as measured by rate and severity of AEs
• To determine the steady state exposure of RAD001 at pre-dose and 1 hour and 2 hours post-dose at the explored combination dose-levels using concentrations at pre-dose (Cmin) and at 1 hour (C1h) and 2 hours (C2h) post-dose
Phase 2
• clinical efficacy in terms of the following endpoints according to RECIST:
• Best overall response
• PFS
• To compare overall survival of RAD001 + sorafenib with sorafenib alone
• safety and tolerability of of RAD001 + sorafenib as measured by rate and severity of AEs
To determine the steady state exposure of RAD001 at pre-dose and 1 hour and 2 hours post-dose at the explored combination dose-levels using concentrations at pre-dose (Cmin) and at 1 hour (C1h) and 2 hours (C2h) post-dose
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Secondary ID(s)
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CRAD001O2101
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date:
Contact:
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