Antiangiogenic Treatment of Hepatocellular Cancer With Bevacizumab and RAD001

NCT00775073 | Completed Phase 2 DMC

• 1 other identifier: CRAD001C24100
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 10

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

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  24 and 48 weeks

Secondary Outcomes (1)

• Overall Survival

  24 and 48 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Bevacizumab (Avastin) \& Everolimus (RAD001)

Drug: Everolimus, Bevacizumab

Interventions

Everolimus, Bevacizumab DRUG

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

Also known as: RAD001, Avastin

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gerhard Treiber: lead
• Crolll Gmbh: collaborator
• Estimate, GmbH: collaborator
• Janssen Diagnostics, LLC: collaborator

Study Sites (10)

Medizinische Klinik 1 University of Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Zollernalbklinikum

Balingen, 72336, Germany

Location

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

Berlin, 13353, Germany

Location

Universitaetsklinikum Bonn, Medizinische Klinik und Poliklinik I

Bonn, 53105, Germany

Location

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

Frankfurt, 60590, Germany

Location

Medizinische Universitaetsklinik Freiburg, Innere Medizin II

Freiburg im Breisgau, 79095, Germany

Location

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

Halle, 06120, Germany

Location

Medizinische Hochschule Hannover, Zentrum Innere Medizin

Hanover, 30625, Germany

Location

Universitätsklinikum des Saarlandes Klinik für Innere medizin II

Homburg/Saar, 66421, Germany

Location

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

Magdeburg, 39120, Germany

Location

Related Publications (1)

• 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.

  PMID: 19192962 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Everolimus; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gerhard Treiber, PD Dr.

  Zollernalbklinikum Balingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: October 16, 2008
• First Posted: October 17, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: April 1, 2012
• Last Updated: April 30, 2012

Record last verified: 2012-04

Locations

DE (10)