NCT00878111

Study of NGR-hTNF Administered at High Doses in Patient With Advanced or Metastatic Solid Tumour

NGR013: Phase I and Pharmacodynamic Study of NGR-hTNF Administered at High Doses in Patients With Advanced or Metastatic Solid Tumour

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: AGC Biologics S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main objective of the trial is to document the safety and antivascular effect of escalating doses of NGR-hTNF, from 60 mcg/sqm to 325 mcg/sqm, in patients affected by advanced or metastatic solid tumors not amenable of standard therapies. Safety will be established by clinical and laboratory assessment according to NCI-CTCAE criteria (version 4.02).

Detailed description

Pre-clinical studies provide the support that NGR-TNF is endowed with a higher therapeutic index in animal models and studies of the mechanism of action showed that NGR-TNF can induce tumour necrosis when used at relatively high doses. Recently, a phase I dose-escalation study of NGR-hTNF has explored the dose range between 0.2 and 60 µg/m2, showing DLT at 60 mcg/m2 experienced as transient acute infusion reaction few minutes after the first administration start. Considering the relationship with the infusion of these events, a further dose escalation will be explored in the present phase I study by using both a longer infusion time (i.e., 120 minutes instead of 60 minutes) and a mild premedication. The first cohort (n=4) of patients will be treated with NGR-hTNF administered at 60 mcg/m2 IV every three weeks, that is a dose level 33% higher than MTD and recommended dose selected in the previous phase I trial (i.e., 45 mcg/m2). If ≤1 of 4 patients experience DLT during the first cycle, following cohorts will be treated with escalating doses (from 80 to 325 mcg/m2) of NGR-hTNF IV every three weeks.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	NGR-hTNF	First cohort: iv q3W 60 mcg/sqm over 120 min\* Second cohort: iv q3W 80 mcg/sqm over 120 min\* Third cohort: iv q3W 100 mcg/sqm over 120 min\* Fourth cohort: iv q3W 125 mcg/sqm over 120 min\* Fifth cohort: iv q3W 150 mcg/sqm over 120 min\* Sixth cohort: iv q3W 175 mcg/sqm over 120 min\* Seventh cohort: iv q3W 200 mcg/sqm over 120 min\* Eighth cohort: iv q3W 225 mcg/sqm over 120 min\* Ninth cohort: iv q3w 250 mcg/sqm over 120 min\* Tenth cohort: iv q3w 275 mcg/sqm over 120 min\* Eleventh cohort: iv q3w 300 mcg/sqm over 120 min\* Twelfth cohort: iv q3w 325 mcg/sqm over 120 min\* \* If the first infusion is well-tolerated, the second infusion may be delivered over 90 minutes. If the 90-minute infusion is well tolerated, all subsequent infusions may be delivered over a 60-minute period.

Timeline

• Start date: 2009-04-01
• Primary completion: 2017-02-01
• Completion: 2017-02-01
• First posted: 2009-04-08
• Last updated: 2018-08-29

Locations

1 site across 1 country: Italy