Study of NGR-hTNF as Single Agent in Patients Affected by Colorectal Cancer (CRC)

• Tumor Growth Control Rate (TGCR) according to RECIST criteria [ Time Frame: during the study ] [ Designated as safety issue: No ]
• Overall survival (OS) [ Time Frame: during the study ] [ Designated as safety issue: No ]
• Circulating tumor cells (CTCs) [ Time Frame: before and following the treatment ] [ Designated as safety issue: No ]
• Experimental imaging study (DCE-MRI) [ Time Frame: before and following the first cycle ] [ Designated as safety issue: No ]
• Pharmacokinetic in patients treated with weekly schedule [ Time Frame: before, during and following the treatment ] [ Designated as safety issue: No ]
• Safety [ Time Frame: during and following the treatment ] [ Designated as safety issue: Yes ]

The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic colorectal cancer patients treated with NGR-hTNF as single agent. Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.

This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic colorectal cancer (CRC), previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens, that will be conducted using Simon's two-stage design method.

Inclusion Criteria:

• Patients >18 years affected by advanced or metastatic colorectal cancer (CRC), previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens, but not more than three lines of therapy. Adjuvant chemotherapy following definitive management of the primary lesion in the colon or rectum is allowed and will not be counted as a line of therapy

  • 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 < 1.5 x ULN
• AST and/or ALT < 2.5 x ULN in absence of liver metastases
• AST and/or ALT < 5 x ULN in presence of liver metastases

• Serum creatinine < 1.5 x ULN

  • Absence of any conditions in which hypervolemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or hemodilution 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 to participate in the study

Exclusion Criteria:

• More than three lines of chemotherapy (except biological agents)
• 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