Study of NGR-hTNF Administered at High Doses in Patient With Advanced or Metastatic Solid Tumour
|ClinicalTrials.gov Identifier: NCT00878111|
Recruitment Status : Unknown
Verified October 2015 by MolMed S.p.A..
Recruitment status was: Active, not recruiting
First Posted : April 8, 2009
Last Update Posted : October 9, 2015
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).
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors||Drug: NGR-hTNF||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NGR013: Phase I and Pharmacodynamic Study of NGR-hTNF Administered at High Doses in Patients With Advanced or Metastatic Solid Tumour|
|Study Start Date :||April 2009|
|Estimated Primary Completion Date :||June 2016|
|Estimated Study Completion Date :||June 2016|
Experimental: A: escalating dose levels of NGR-hTNF
NGR-hTNF administered at high doses
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.
- Optimal Biologic Dose (OBD) [ Time Frame: Before treatment, every 3-6 wks and end of treatment ]Evaluating both the safety in terms of maximum tolerated dose (MTD) and the antivascular effect in terms of changes documented with dynamic imaging (DCE-MRI)
- Pharmacokinetic [ Time Frame: Several time points after 1^st, 2^nd and 3^rd administration ]Evaluation of plasma levels of sTNF-RI and sTNF-RII and anti-NGR-hTNF antibodies
- Preliminary antitumor activity [ Time Frame: Every 6 wks ]In terms of objective response rate according to RECIST criteria, progression-free and overall survival.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00878111
|Istituto Clinico Humanitas|
|Rozzano, Milan, Italy, 20089|
|Study Director:||Antonio Lambiase, MD||MolMed S.p.A.|