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

A Phase IB Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic 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.

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