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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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NGR006: A Phase II Study of NGR-hTNF Administered as Single Agent Every 3 Weeks or Weekly in Patients Affected by Colorectal Cancer (CRC), Previously Treated With Fluoropyrimidine, Oxaliplatin and Irinotecan Based Regimens

Conditions
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Colorectal Cancer (CRC)

Intervention / Treatment
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* Drug: NGR-hTNF


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: NGR-hTNF<br>NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every 3 weeks or weekly | Drug: NGR-hTNF<br>* iv q3W or q1W NGR-hTNF 0.8 μg/m²<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS evaluated according to Response evaluation criteria in solid tumors (RECIST) | during the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Growth Control Rate (TGCR) | TGCR evaluated according to Response evaluation criteria in solid tumors (RECIST) | during the study | 
| Overall survival (OS) | Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive | during the study | 
| Circulating tumor cells (CTCs) | To document modification of CTCs | before and following the treatment | 
| Experimental imaging study (DCE-MRI) | to document possible modifications on vessels permeability | before and following the first cycle | 
| to evaluate AUC(tau) of NGR-hTNF in patients treated with weekly schedule | to evaluate AUC(tau) of NGR-hTNF administered weekly | during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start) | 
| to evaluate Cmax of NGR-hTNF in patients treated with weekly schedule | to evaluate Cmax of NGR-hTNF administered weekly | during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start) | 
| Safety according to NCI-CTCAE criteria (version 3) | To evaluate safety profile related to NGR-hTNF | during and following the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGR-hTNF, CRC