Antiangiogenic Treatment of Hepatocellular Cancer With Bevacizumab and RAD001

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00775073
• Other study ID #: CRAD001C24100
• Status: Completed
• Phase: Phase 2
• First received: October 16, 2008
• Last updated: April 27, 2012
• Start date: October 2008
• Est. completion date: April 2012

Study information

• Verified date: April 2012
• Source: Treiber, Gerhard
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: April 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Neoplasms

Intervention

Drug:
• Everolimus, Bevacizumab
Everolimus 5 mg tablet per day orally. Bevazicumab 5 mg per kg intravenous every 2 weeks.

Locations

Country	Name	City	State
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	Medizinische Klinik 1 University of Erlangen	Erlangen	Bavaria
Germany	Klinikum der J.-W.-Goethe-Universitaet, Medizinische Klinik I	Frankfurt
Germany	Medizinische Universitaetsklinik Freiburg, Innere Medizin II	Freiburg
Germany	Martin-Luther-Universitaet Halle-Wittenberg, Universitaetsklinik und Poliklinik für Innere Medizin I	Halle
Germany	Medizinische Hochschule Hannover, Zentrum Innere Medizin	Hannover
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

Sponsors (4)

Lead Sponsor	Collaborator
Gerhard Treiber	Crolll Gmbh, Estimate, GmbH, Janssen Diagnostics, LLC

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Progression		24 and 48 weeks	Yes
Secondary	Overall Survival		24 and 48 weeks	Yes