Antiangiogenic Treatment of Hepatocellular Cancer With Bevacizumab and RAD001

NCT ID: NCT00775073

Last Updated: 2012-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-04-30

Brief Summary

This is a prospective open label clinical trial in patients with advanced or metastatic liver cancer to assess the clinical and biological activity of RAD001 (Everolimus) in conjunction with Bevazicumab (Avastin). Approximately 36 patients will be enrolled.

Conditions

Hepatocellular Carcinoma

Keywords

Liver cancer; HCC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Bevacizumab (Avastin) \& Everolimus (RAD001)

Group Type: EXPERIMENTAL

Everolimus, Bevacizumab

Intervention Type: DRUG

Everolimus 5 mg tablet per day orally. Bevazicumab 5 mg per kg intravenous every 2 weeks.

Interventions

Everolimus, Bevacizumab

Everolimus 5 mg tablet per day orally. Bevazicumab 5 mg per kg intravenous every 2 weeks.

Intervention Type: DRUG

Other Intervention Names

RAD001; Avastin

Eligibility Criteria

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 capsules/tablets)

• 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 diverticulitis
• Any relevant findings on screening colonoscopy
• History of any thromboembolic events (except for portal vein infiltration and/or thrombosis)
• 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 randomisation
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Crolll Gmbh

OTHER

Sponsor Role: collaborator

Estimate, GmbH

INDUSTRY

Sponsor Role: collaborator

Janssen Diagnostics, LLC

INDUSTRY

Sponsor Role: collaborator

Gerhard Treiber

INDIV

Sponsor Role: lead

Responsible Party

Gerhard Treiber

Prof. Dr. med.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gerhard Treiber, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

Zollernalbklinikum Balingen

Locations

Medizinische Klinik 1 University of Erlangen

Erlangen, Bavaria, Germany

Zollernalbklinikum

Balingen, , Germany

Charité, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie

Berlin, , Germany

Universitaetsklinikum Bonn, Medizinische Klinik und Poliklinik I

Bonn, , Germany

Klinikum der J.-W.-Goethe-Universitaet, Medizinische Klinik I

Frankfurt, , Germany

Medizinische Universitaetsklinik Freiburg, Innere Medizin II

Freiburg im Breisgau, , Germany

Martin-Luther-Universitaet Halle-Wittenberg, Universitaetsklinik und Poliklinik für Innere Medizin I

Halle, , Germany

Medizinische Hochschule Hannover, Zentrum Innere Medizin

Hanover, , Germany

Universitätsklinikum des Saarlandes Klinik für Innere medizin II

Homburg/Saar, , Germany

Medizinische Fakultaet der Otto-von-Guericke-Universitaet, Klinik für Gastroenterologie, Hepatologie und Infektiologie

Magdeburg, , Germany

Countries

Germany

References

Treiber G. mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther. 2009 Feb;9(2):247-61. doi: 10.1586/14737140.9.2.247.

Reference Type: DERIVED

PMID: 19192962 (View on PubMed)

Other Identifiers

CRAD001C24100

Identifier Type: -

Identifier Source: org_study_id