Antiangiogenic Treatment of Hepatocellular Cancer With Bevacizumab and RAD001

April 27, 2012 updated by: Gerhard Treiber

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Balingen, Germany, 72336
        • Zollernalbklinikum
      • Berlin, Germany, 13353
        • Charité, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie
      • Bonn, Germany, 53105
        • Universitaetsklinikum Bonn, Medizinische Klinik und Poliklinik I
      • Frankfurt, Germany, 60590
        • Klinikum der J.-W.-Goethe-Universitaet, Medizinische Klinik I
      • Freiburg, Germany, 79095
        • Medizinische Universitaetsklinik Freiburg, Innere Medizin II
      • Halle, Germany, 06120
        • Martin-Luther-Universitaet Halle-Wittenberg, Universitaetsklinik und Poliklinik für Innere Medizin I
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover, Zentrum Innere Medizin
      • Homburg/Saar, Germany, 66421
        • Universitätsklinikum des Saarlandes Klinik für Innere medizin II
      • Magdeburg, Germany, 39120
        • Medizinische Fakultaet der Otto-von-Guericke-Universitaet, Klinik für Gastroenterologie, Hepatologie und Infektiologie
    • Bavaria
      • Erlangen, Bavaria, Germany, 91054
        • Medizinische Klinik 1 University of Erlangen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Bevacizumab (Avastin) & Everolimus (RAD001)
Drug: Everolimus, Bevacizumab
Everolimus 5 mg tablet per day orally. Bevazicumab 5 mg per kg intravenous every 2 weeks.
Other Names:
  • Avastin
  • RAD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to Progression
Time Frame: 24 and 48 weeks
24 and 48 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 24 and 48 weeks
24 and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gerhard Treiber

Collaborators

Crolll Gmbh
Janssen Diagnostics, LLC
Estimate, GmbH

Investigators

  • Principal Investigator: Gerhard Treiber, PD Dr., Zollernalbklinikum Balingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

October 16, 2008

First Submitted That Met QC Criteria

October 16, 2008

First Posted (Estimate)

October 17, 2008

Study Record Updates

Last Update Posted (Estimate)

April 30, 2012

Last Update Submitted That Met QC Criteria

April 27, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001C24100

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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