Study of NGR-hTNF in Combination With Doxorubicin in Solid Tumors
Condition: Cancer
Intervention: NGR-hTNF; Doxorubicin
Intervention description: 0.2, 0.4, 0.8 and 1.6 μg/m²as 60-minute intravenous infusion every 3 weeks; 75 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion)
Intervention MeSH terms: Doxorubicin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose-escalating study
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NGR-hTNF; doxorubicin; solid tumors

Summary:

      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 ).
    

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