Antiangiogenic Treatment of Hepatocellular Cancer With Bevacizumab and RAD001

This study has been completed.
Sponsor:
Collaborators:
Crolll Gmbh
estimate GmbH, Augsburg
Janssen Diagnostics, LLC
Information provided by (Responsible Party):
Gerhard Treiber, Treiber, Gerhard
ClinicalTrials.gov Identifier:
NCT00775073
First received: October 16, 2008
Last updated: April 27, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Everolimus, Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antiangiogenic Treatment of Advanced or Metastatic Hepatocellular Cancer (HCC) - An Open Label, Stratified, Single-arm Phase II Study of Bevacizumab and RAD001

Resource links provided by NLM:


Further study details as provided by Treiber, Gerhard:

Primary Outcome Measures:
  • Time to Progression [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 33
Study Start Date: October 2008
Study Completion Date: April 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • RAD001
  • Avastin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775073

Locations
Germany
Medizinische Klinik 1 University of Erlangen
Erlangen, Bavaria, Germany, 91054
Zollernalbklinikum
Balingen, Germany, 72336
Charité, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie
Berlin, Germany, 13353
Universitaetsklinikum Bonn, Medizinische Klinik und Poliklinik I
Bonn, Germany, 53105
Klinikum der J.-W.-Goethe-Universitaet, Medizinische Klinik I
Frankfurt, Germany, 60590
Medizinische Universitaetsklinik Freiburg, Innere Medizin II
Freiburg, Germany, 79095
Martin-Luther-Universitaet Halle-Wittenberg, Universitaetsklinik und Poliklinik für Innere Medizin I
Halle, Germany, 06120
Medizinische Hochschule Hannover, Zentrum Innere Medizin
Hannover, Germany, 30625
Universitätsklinikum des Saarlandes Klinik für Innere medizin II
Homburg/Saar, Germany, 66421
Medizinische Fakultaet der Otto-von-Guericke-Universitaet, Klinik für Gastroenterologie, Hepatologie und Infektiologie
Magdeburg, Germany, 39120
Sponsors and Collaborators
Gerhard Treiber
Crolll Gmbh
estimate GmbH, Augsburg
Janssen Diagnostics, LLC
Investigators
Principal Investigator: Gerhard Treiber, PD Dr. Zollernalbklinikum Balingen
  More Information

No publications provided by Treiber, Gerhard

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gerhard Treiber, Prof. Dr. med., Treiber, Gerhard
ClinicalTrials.gov Identifier: NCT00775073     History of Changes
Other Study ID Numbers: CRAD001C24100
Study First Received: October 16, 2008
Last Updated: April 27, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Treiber, Gerhard:
Liver cancer
HCC

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Bevacizumab
Angiogenesis Inhibitors
Sirolimus
Everolimus
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on October 01, 2014