Antiangiogenic Treatment of Hepatocellular Cancer With Bevacizumab and RAD001

Sponsor

Gerhard Treiber (Other)

Overall Status

Completed

CT.gov ID

NCT00775073

Collaborator

Crolll Gmbh (Other), Estimate, GmbH (Industry), Janssen Diagnostics, LLC (Industry)

Enrollment

Locations

Arm

Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Everolimus, Bevacizumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Jan 1, 2011

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

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: RAD001 Avastin

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:

RAD001

Avastin

Outcome Measures

Primary Outcome Measures

Time to Progression [24 and 48 weeks]

Secondary Outcome Measures

Overall Survival [24 and 48 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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