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

NCT00878111 | Completed Phase 1

• 2 other identifiers: NGR0132008-000816-33
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Solid Tumors

Keywords

NGR-hTNF; Solid tumours; High doses

Outcome Measures

Primary Outcomes (1)

• Optimal Biologic Dose (OBD)

  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)

  Before treatment, every 3-6 weeks and at the end of treatment

Secondary Outcomes (2)

• Pharmacokinetic

  Several time points after 1st, 2nd and 3rd administration

• Preliminary antitumor activity

  Every 6 weeks

Study Arms (1)

A: escalating dose levels of NGR-hTNF

EXPERIMENTAL

NGR-hTNF administered at high doses

Drug: NGR-hTNF

Interventions

NGR-hTNF DRUG

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.

A: escalating dose levels of NGR-hTNF

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 with selected metastatic solid tumours recognized to be highly vascularised and not amenable to any clinical improvement by current standard treatments
• Colorectal cancer (CRC) patients previously resistant to standard systemic regimens (including biologic agents)
• Gastric cancer (GC) patients treated with no more than two standard systemic regimens for metastatic disease
• Hepatocellular carcinoma (HCC) patients previously resistant to standard systemic regimens
• Pancreatic carcinoma (PC) patients treated with no more than one standard systemic regimen for metastatic disease
• Non small cell lung carcinoma (NSCLC) patients treated with no more than two standard systemic regimens (including biologic agents) for metastatic disease
• Neuroendocrine (NE) tumours refractory to somatostatin analogue treatment
• Other rare tumours including malignant pleural mesothelioma (MPM), soft-tissue sarcoma (STS), and renal cell carcinoma (RCC), resistant/refractory to current standard treatments
• Life expectancy more than 3 months
• ECOG Performance status 0-1
• 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 metastasis
• AST and/or ALT \<5 x ULN in presence of liver metastasis

You may not qualify if:

• Concurrent anticancer therapy
• Patients must not receive any other investigational agents while on study
• Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
• Uncontrolled hypertension
• Prolonged QTc interval (congenital or acquired) \> 450 ms
• Patient with significant peripheral vascular disease
• History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy), or history of stroke
• 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 or contraindications 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 child-bearing 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)

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

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: April 7, 2009
• First Posted: April 8, 2009
• Study Start: April 1, 2009
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: August 29, 2018

Record last verified: 2018-08

Locations

IT (1)