Study of NGR-hTNF in Combination With Doxorubicin in Solid Tumors

The main objective of the trial is to document the safety of the combination (escalation doses of NGR-hTNF, from 0.2 mcg/sqm to 1.6 mcg/sqm , with a fixed dose of doxorubicin, 75 mg/sqm). Safety will be established by clinical and laboratory assessment according to National Cancer Institute Common Toxicity Criteria (NCI-CTC ).

This is a phase IB, open-label, non-randomized, dose-escalation study that will be conducted in sequential cohorts of patients. Three patients per each cohort are planned.

Patients, with advanced or metastatic solid tumor previously treated with a non cumulative dose of doxorubicin (\<300 mg/sqm in order to allow an adequate number of cycles) or chemotherapy naïve will be enrolled.

Eligibility Criteria:
Inclusion Criteria:

* Patients ≥18 years old with proven advanced or metastatic solid tumor not amenable to any clinical improvement by current standard treatments and previously treated with a non cumulative dose of anthracyclines (\<300 mg/sqm) or chemotherapy naïve.
* Life expectancy more than 3 months.
* ECOG performance status 0 - 2.
* Normal cardiac function (left ventricular ejection fraction \[LVEF\] ≥55%) and absence of uncontrolled hypertension.
* Absence of any conditions involving hypervolemia and its consequences.
* 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 \< 1.5 x ULN AST and/or ALT \< 2 x ULN Serum creatinine \< 1.5 x ULN

* Patients may have had prior therapy providing the following conditions are met:

  * Chemo, radio, hormonal, immuno or anti-vascular therapy: wash-out period of 28 days.
  * Surgery: wash-out period of 14 days.
* Patients must give written informed consent to participate in the study.

Exclusion Criteria:

* Concurrent anticancer therapy
* Patients must not receive any other investigational agents while on study
* Patients with a LVEF \<55%
* New York Heart Association class III or IV cardiac disease
* Acute angina
* Patients with myocardial infarction within the last six (6) months
* Patient with significant peripheral vascular disease
* Thrombosis of main portal vein
* Previous signs of severe toxicity doxorubicin related
* Previous signs of cardiotoxicity doxorubicin related
* Patients previously treated with a cumulative dosage of anthracyclines ≥300 mg/m\^2
* 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 child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration