A Modified Phase I Study of NGR-hTNF in Advanced Solid Tumors

Study Overview
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Brief Summary
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The main objective of the trial is to explore the safety and biological activity of NGR-hTNF. The safety will be established by clinical and laboratory assessment. The biological activity will be evaluated by DCE-MRI with contrast media.

Detailed Description
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This is a modified phase I Single arm, open, non randomized trial of NGR-hTNF in advanced solid tumors for the definition of an optimal biological

Official Title
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NGR002: A Modified Phase I Study of NGR-hTNF in Advanced Solid Tumors: Definition of an Optimal Biological Dose

Conditions
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Advanced Solid Tumors

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 old with proven advanced solid tumors not amenable to any clinical improvement by current standard treatments. Tumors recognized to be highly vascularized (e.g. renal, colon thyroid and head and neck cancers), will be included. ECOG Performance status 0 - 2 Patients may have had prior therapy providing the following conditions are met: Chemo, radio, hormonal or immunotherapy: wash-out period of 28 days Surgery: wash-out period of 14 days 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 haemodilution 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: 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

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: Experimental Arm A<br>Patients were scheduled to receive a 1 hour intravenous (iv) infusion of NGR-hTNF every 3weeks.- The dose of administered NGR-hTNF was: 0.2, 0.4, 0.8, 1.6 μg/m2 (step 1); 3.2, 6.4, 12.8 μg/m2 (step 2); 19.2, 28.8, 43.2 64.8 μg/m2 (step 3); 86.2, 114.6, 152.4 μg/m2 (step 4) | Drug: NGR-hTNF<br>* Drug: NGR-hTNF NGR-hTNF was administered every 3 weeks by a 1 hour intravenous iv infusion. NGR-hTNF in PBS was diluted in 0.9% NaCl, containing human serum albumin. Step 1: starting dose: 0.2 μg/m2 following doses: 0.4, 0.8 and 1.6 μg/m2. number of patients: 4 per dose level Step 2: starting dose: 3.2 μg/m2 following doses: 6.4 and 12.8 μg/m2 number of patients: 3 per dose level Step 3: starting dose: 19.2 μg/m2 following doses: 28.8, 43.2 and 64.8 μg/m2 number of patients: 3 per dose level Step 4: starting dose: 86.2 μg/m2 following doses: 114.6 and 152.4 μg/m2 number of patients: 3 per dose level<br>* Other names: iv q3W escalating dose up 1.6 mcg/sqm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To verify safety of escalating doses of NGR-hTNF | To verify safety of escalating doses of NGR-hTNF | during and following the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To document possible modifications on vessels permeability | To document possible modifications on vessels permeability | before and following the first treatment | 
| To document signs of anticancer activity | To document signs of anticancer activity | every 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumors NGR-hTNF