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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00419328
• Other study ID #: NGR002
• Secondary ID: 2004-002194-23
• Status: Completed
• Phase: Phase 1
• Start date: March 2005
• Est. completion date: September 2007

Study information

• Verified date: January 2013
• Source: AGC Biologics S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Italy	Fondazione San Raffaele del Monte Tabor	Milan

Sponsors (1)

Lead Sponsor	Collaborator
AGC Biologics S.p.A.

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To verify safety of escalating doses of NGR-hTNF	To verify safety of escalating doses of NGR-hTNF	during and following the treatment
Secondary	To document possible modifications on vessels permeability	To document possible modifications on vessels permeability	before and following the first treatment
Secondary	To document signs of anticancer activity	To document signs of anticancer activity	every 6 weeks