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

NCT00419328 | Completed Phase 1

• 2 other identifiers: NGR0022004-002194-23
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors

Keywords

solid tumors NGR-hTNF

Outcome Measures

Primary Outcomes (1)

• To verify safety of escalating doses of NGR-hTNF

  To verify safety of escalating doses of NGR-hTNF

  during and following the treatment

Secondary Outcomes (2)

• To document possible modifications on vessels permeability

  before and following the first treatment

• To document signs of anticancer activity

  every 6 weeks

Study Arms (1)

Experimental Arm A

EXPERIMENTAL

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

Interventions

NGR-hTNF 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

Also known as: iv q3W escalating dose up 1.6 mcg/sqm

Experimental Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (1)

Fondazione San Raffaele del Monte Tabor

Milan, Italy

Location

Related 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 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.

  PMID: 19900802 RESULT

MeSH Terms

Interventions

tumor necrosis factor-alpha, CNGRC fusion protein, human

Study Officials

• Antonio Lambiase, MD

  AGC Biologics S.p.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2007
• First Posted: January 8, 2007
• Study Start: March 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: July 21, 2022

Record last verified: 2013-01

Locations

IT (1)