Know Cancer

forgot password

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

Phase 1
18 Years
Open (Enrolling)
Solid Tumors

Thank you

Trial Information

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

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.

Inclusion Criteria:

- Patients ≥18 years with selected metastatic solid tumours recognized to be highly
vascularised and not amenable to any clinical improvement by current standard

- 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

- Serum creatinine <1.5 x ULN

- Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50

- Patients may have had prior therapy providing the following conditions are met before
treatment start:

- Chemotherapy, radiation therapy, hormonal therapy, or immunotherapy: wash-out
period of 28 days

- Surgery: wash-out period of 14 days

- Patients must give written informed consent to participate in the study.

Exclusion Criteria:

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimal Biologic Dose (OBD)

Outcome Description:

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)

Outcome Time Frame:

Before treatment, every 3-6 wks and end of treatment

Safety Issue:


Principal Investigator

Antonio Lambiase, MD

Investigator Role:

Study Director

Investigator Affiliation:

MolMed S.p.A.


Italy: National Institute of Health

Study ID:




Start Date:

April 2009

Completion Date:

June 2013

Related Keywords:

  • Solid Tumors
  • NGR-hTNF
  • Solid tumours
  • High doses
  • Neoplasms