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Antiangiogenic Treatment of Advanced or Metastatic Hepatocellular Cancer (HCC) - An Open Label, Stratified, Single-arm Phase II Study of Bevacizumab and RAD001

Phase 2
18 Years
Not Enrolling
Hepatocellular Carcinoma

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Trial Information

Antiangiogenic Treatment of Advanced or Metastatic Hepatocellular Cancer (HCC) - An Open Label, Stratified, Single-arm Phase II Study of Bevacizumab and RAD001

Inclusion Criteria:

- Age >18 years

- 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

- 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

- Confirmation of HCC disease by histology (preceding liver resection or fine needle
biopsy within the last 12 months);

- Liver Function: Child A and B

- Tumor extent: CLIP Score ≤ 3

- ECOG Performance Status 0-2 (=Karnofsky-Index ≥ 60%)

Exclusion Criteria:

- 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)

- Patient had a major surgery, local ablative treatments (RFA, PEI), or transarterial
chemoembolisation therapy within 4 weeks prior to randomisation

- 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.

- History or presence of central nervous system (CNS) disease (i.e., primary brain
tumor, malignant seizures, CNS metastases or carcinomatous meningitis) or other
mental illness.

- Clinically serious infections or uncontrolled infection (including HIV infection),
increased risk for acquisition of opportunistic infections

- Chronic treatment with systemic steroids or another immunosuppressive agent

- Inadequate 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 <
2.5 g/dl, renal impairment (serum creatinine < 1.5 x UNL ), inadequate Hematology:
Platelets < 75.000, ANC < 1500, hemoglobin < 9.0 mg/dl, inadequate coagulation
status, namely INR > 2 or Quick < 50%, aPTT >50 sec in the absence of any drugs
interfering with coagulation such as warfarin, phenprocoumon, NMH or UFH. 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

- Women who are pregnant or breast feeding, intended pregnancy, or women unable to
conceive and unwilling to practice an effective method of birth control

- Impairment of gastrointestinal (GI) 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

Exclusion Criteria derived from special situations:

- Mixed tumors of HCC with cholangiocarcinoma or fibrolamellar HCC type

- Patients with complications of liver cirrhosis such as recent spontaneous bacterial
infection of ascites, hepatic encephalopathy > grade 2 during the last 2 weeks and
not adequately controlled or hepatorenal syndrome not responding to conservative
treatment within 2 weeks

- Patients with any active gastrointestinal bleeding during the last 2 weeks

- Patients without screening EGD during the last 2 weeks

- Patients with nonbleeding gastroesophageal varices grade I° with red coloured signs
or grade ≥ II° on EGD that do not undergo prophylactic ligation or sclerosing
treatment at least one week before the first dose of study medication is taken.

- Patients with unhealed gastrointestinal ulcerations or wounds

- Patients with a history of one of the following: bowel perforation, colon

- Any relevant findings on screening colonoscopy

- History of any thromboembolic events (except for portal vein infiltration and/or

- Allergic reactions or intolerance to previous drug exposure to RAD001 or bevacizumab;
having received any of the study medications within the last 3 years before

- Allergy or intolerance against CHO-cell products or other recombinant human or
humanised antibodies

- Patients with an increased risk for the development of lymphoma or other malignant
diseases, especially concerning the skin

- Patients with rare hereditary disorders like galactose intolerance, lactase
deficiency or glucose-galactose malabsorption

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to Progression

Outcome Time Frame:

24 and 48 weeks

Safety Issue:


Principal Investigator

Gerhard Treiber, PD Dr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Zollernalbklinikum Balingen


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

October 2008

Completion Date:

April 2012

Related Keywords:

  • Hepatocellular Carcinoma
  • Liver cancer
  • HCC
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular