Clinical trial NCT00484211: Study of NGR-hTNF as Single Agent in Patients Affected by Advanced or Metastatic Hepatocellular Carcinoma (HCC)
Official title: NGR008: A Phase II Study of NGR-hTNF Administered as Single Agent Every 3 Weeks or Weekly in Patients Affected by Advanced or Metastatic Hepatocellular Carcinoma (HCC) Previously Treated With no More Than One Systemic Therapeutic Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: NGR-hTNF, Hepatocellular Carcinoma (HCC)
Lead sponsor: AGC Biologics S.p.A.
Sponsor class: INDUSTRY
First posted: 2007-06-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic hepatocellular carcinoma patients treated with NGR-hTNF as single agent.

Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria

Detailed description: This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic Hepatocellular Carcinoma (HCC) previously treated with no more than one systemic therapeutic regimen, that will be conducted using Simon's two-stage design method.

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years affected by advanced or metastatic HCC previously treated with no more than one systemic therapeutic regimen
* Histologically confirmed HCC not amenable to curative surgery
* Child-Pugh scale class A
* ECOG Performance status 0 - 1
* Patients in progression disease at study entry CT documented
* Adequate baseline bone marrow, hepatic and renal function, defined as follows:

  * Neutrophils \> 1.5 x 10\^9/L and platelets \> 100 x 10\^9/L
  * Bilirubin \< 2 x ULN
  * Transaminases \< 3 x ULN
* Absence of any conditions in which hypervolaemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (reference appendix "Technical data sheet human albumin")
* Normal cardiac function and absence of uncontrolled hypertension
* Patients must give written informed consent

Exclusion criteria:

* Decompensated cirrhosis (Child-Pugh score \>7)
* Concurrent anticancer therapy
* Patients may not receive any other investigational agents while on study
* Clinical signs of CNS involvement
* Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
* Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
* Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Primary outcomes:
measure: Antitumour activity defined as progression free survival (PFS)
timeFrame: during the study
Secondary outcomes:
measure: Tumor growth control rate (TGCR) according to WHO criteria
timeFrame: during the study
measure: Pharmacokinetics in patients treated with weekly schedule
timeFrame: during treatment
measure: Safety
timeFrame: during the study
measure: Overall survival (OS)
timeFrame: During the treatment and during the follow-up
measure: Experimental imaging study (DCE-MRI)
timeFrame: During the treatment
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Milan
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
city: Milan
country: Italy
facility: Istituto Europeo Oncologico
Study officials:
affiliation: AGC Biologics S.p.A.
name: Antonio Lambiase, MD
role: STUDY_DIRECTOR
References:
citation: Santoro A, Pressiani T, Citterio G, Rossoni G, Donadoni G, Pozzi F, Rimassa L, Personeni N, Bozzarelli S, Rossoni G, Colombi S, De Braud FG, Caligaris-Cappio F, Lambiase A, Bordignon C. Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma. Br J Cancer. 2010 Sep 7;103(6):837-44. doi: 10.1038/sj.bjc.6605858. Epub 2010 Aug 17.