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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: NGR-hTNF

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Fondazione San Raffaele del Monte Tabor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental Arm A; 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; 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; Other Names: iv q3W escalating dose up 1.6 mcg/sqm

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AGC Biologics S.p.A.

Publications and helpful links

General Publications

• Gregorc V, Citterio G, Vitali G, Spreafico A, Scifo P, Borri A, Donadoni G, Rossoni G, Corti A, Caligaris-Cappio F, Del Maschio A, Esposito A, De Cobelli F, Dell'Acqua F, Troysi A, Bruzzi P, Lambiase A, Bordignon C. Defining the optimal biological dose of NGR-hTNF, a selective vascular targeting agent, in advanced solid tumours. Eur J Cancer. 2010 Jan;46(1):198-206. doi: 10.1016/j.ejca.2009.10.005.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: January 5, 2007
• First Submitted That Met QC Criteria: January 5, 2007
• First Posted (Estimate): January 8, 2007

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: solid tumors NGR-hTNF
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NGR002; 2004-002194-23 (EudraCT Number)