Antiangiogenic Treatment of Advanced or Metastatic Hepatocellular Cancer (HCC) MedDRA version: 9.1 Level: LLT Classification code 10049010 Term: Carcinoma hepatocellular
Conditions
Interventions
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)
Concentrati
Sponsors
PD Dr. Gerhard Treiber
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >18 years 2. Patients with non-resectable locally advanced or metastatic hepatocellular cancer BCLC stage B and C. BCLC stage A can occasionally be included provided that other treatment options are unavailable: they can be denied by the patient, have been performed with documented disease progression or cannot be carried out for other resons such as comorbidities 3. Measurable disease: At least one measurable lesion (longest diameter = 20 mm on conventional CT or MRI scan; = 10 mm on spiral CT) according to RECIST criteria that has not been previously locally treated by irradiation, surgery, ethanol injection, radiofrequency ablation or transarterial chemoembolisation. If the patient has had any previous local treatment to the marker lesion(s), there must be evidence of progression since then. The last scans should be approximately = 4 weeks old before randomisation to be used as baseline scans. 4. Confirmation of HCC disease by histology (preceeding liver resection or fine needle biopsy within the last 12 months); 5. Liver Function: Child A and B 6. Tumor extent: CLIP Score = 3 7. ECOG Performance Status 0-2 (=Karnofsky-Index = 60%) 8. No mental illness that prevent patients from comprehensiveness, written informed consent 9. Written, voluntary informed consent 10. Compliant patient, regular follow-up possible 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
Exclusion criteria: 1. Participation in another clinical trial at the same time or = during the last 4 weeks 2. Patient had received any prior systemic treatment (possible exception: sorafenib for a maximum of 3 months, last dose received at least 28 days before study inclusion) 3. Pat. has received any other investigational agents within 28 days of first day of study drug dosing 4. Pat. had a major surgery, local ablative treatments (RFA, PEI), or transarterial chemoembolisation therapy within 4 weeks prior to randomisation 5. Pat. with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent. 6. Further, if the patient is unable to refrain from alcohol or other substance abuses or any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study 7. Presence of a secondary malignancy either at the time of screening or in the past 5 years: An exception from this rule can be made in patients that were treated in curative intention within the last 3 years and are without any evidence of recurrence of this malignancy. 8. History or presence of central nervous system disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis) or other mental illness. 9. Clinically serious infections or uncontrolled infection (including HIV infection), increased risk for acquisition of opportunistic infections 10. Chronic treatment with systemic steroids or another immunosuppressive agent; interactions with other drugs interfering with the CYP3A4 system should be avoided but can be permitted under circumstances of clinical need and close patient monitoring, provided that the medication used will be kept constant over the first 24 weeks of treatment 11. Indequate organ functions, characterised by: cholestasis with elevated levels of bilirubin and/or alkaline phosphatase > 3x UNL (can be improved by biliary drainage if necessary) and/or elevated transaminases (ALAT/ASAT) = 5 x UNL, hypoalbuminemia 2 or Quick 50 sec in the absence of any drugs interfering with coagulation such as warfarin, phenprocoumone, NMH or UFH. Low-dose aspirin up to 100 mg/d or clopidogrel up to 75 mg/d are permitted together with obligatory prophylactic proton-pump-inhibitor treatment; Fasting serum cholesterol =300 mg/dL OR 7.75 mmol/L AND fasting triglycerides = 2.5 x ULN, patients with severe refractory therapy-resistant hyperlipidemia 12. Women who are pregnant or breast feeding, intended pregnancy, or women unable to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study 13. Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of RAD001 and cannot be controlled by adequate medical treatment (e.g. uncontrolled nausea, vomiting, diarrhoea which might result in malabsorption, any known malabsorption syndrome, bowel obstruction, or inability to swallow the tablets) Criteria derived from special situations: -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Time-to-Progression;Primary end point(s): Time-to-Progression;Secondary Objective: Overall Survival at 24 and 48 weeks Tumor Response according to modified RECIST criteria within the first 24 (-48) weeks of treatment Time-to-Symptomatic Progression (TTSP) Pharmacokinetics of RAD 001 depending on liver function (in subset of patients) Changes in Biomarkers: - tumor markers (AFP, s-IL2, PIVKA-II) - angiogenesis markers (plasma VEGF-A, PDGF-BB, bFGF, sE-SEL, IGF-1) - markers of circulating tumor cells and endothelial cells (CEC, CTC) Predictive Factors for Treatment Response by baseline/follow-up evaluation of tumor tissue by means of IHC (phosphorylated mTOR and S6K protein expression) and PCR microarray (pathway specific gene selection) Safety and Tolerability of RAD001/Bevacizumab | — |
Countries
Germany
Outcome results
None listed