A FEASIBILITY STUDY EVALUATING THE EFFICACY AND SAFETY OF SORAFENIB IN PATIENTS WITH ADVANCED HEPATOCELLULAR (HCC) CARCINOMA AND HIV INFECTION TREATED WITH HAART REGIMENS - sorafenib-HAART

• Conditions: HIV-positive patients with advanced HCC; MedDRA version: 14.1Level: LLTClassification code 10036706Term: Primary liver cancer non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10008919Term: Chronic HIV infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-023602-12-IT
• Lead Sponsor: CENTRO DI RIFERIMENTO ONCOLOGICO DI AVIANO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1.HIV infection serologically proven
2.HCC cytologically/histologically proven or diagnosed according to AASLD guidelines for whom invasive treatment modalities (resection, loco-regional therapies) are not indicated (57).
3.Child–Pugh score A and B7
4.Age = 18 years
5.ECOG Performance Status = 2
6.Life expectancy of at least 12 weeks
7.Presence at least of one measurable lesion according to mRECIST criteria (95). Lesions must be measured by CT-scan or MRI.
8.CD4 counts > 100 cells/µL and HIV viral load < 50 copies/mL
9.Adequate bone marrow, liver and renal function as assessed by the following laboratory measurements, to be conducted within 7 days prior to screening:
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
2.Active clinically serious infections (> grade 2 NCI-CTC version 4.0)
3.Active AIDS-defining infections within the last 6 months or other active AIDS-defining diseases (according to CDC Classification system for HIV infection) including patients with Kaposi sarcoma
4.Patients with CD4 counts < 100 cells/ µL and/or HIV infection that has full drug resistance to any class
5.NNRTI-based HAART or Atazanavir or Tipranavir PI-based HAART
6.Hepatic encephalopathy = CTC G2
7.Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
8.Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
9.History of organ allograft or autologous transplant
10.Patients with evidence or history of bleeding diathesis
11.Patients with clinically significant GI bleeding within 30 days prior to study entry
12.Renal failure requiring dialysis
13.Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy and safety of sorafenib in HCC patients with HIV receiving PI-based HAART regimens.;Primary end point(s): The primary efficacy endpoint is Time to Progression (TTP). TTP will be evaluated according to mRECIST criteria(95) in all patients treated in Step A and Step B.;Secondary Objective: To assess:<br>STEP A and STEP B:<br>•Overall Survival <br>•OS rate at 6 months<br>•Evaluation of Response Rate (RR)<br>• Evaluation of impact on HIV infection (HIV-RNA viral load, CD4-CD8 counts)<br>•Evaluation of Quality of life (FACT-Hep)<br>•Evaluation of the role of innate immunity (receptors of NK and TNK cells) and adaptive immunity (interferon-class I and immuno-complexes) in relationship to clinical response and HCV viral load in HCV co-infected patients.<br>•Evaluation of serum proteomic profile and 2D-DIGE approaches in relationship to drug toxicity and clinical response