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

NCT ID: NCT00419328

Last Updated: 2022-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2007-09-30

Brief 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.

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

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

NGR-hTNF

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

iv q3W escalating dose up 1.6 mcg/sqm

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AGC Biologics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lambiase, MD

Role: STUDY_DIRECTOR

AGC Biologics S.p.A.

Locations

Fondazione San Raffaele del Monte Tabor

Milan, , Italy

Countries

Italy

References

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.

Reference Type: RESULT

PMID: 19900802 (View on PubMed)

Other Identifiers

2004-002194-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGR002

Identifier Type: -

Identifier Source: org_study_id