Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

NGR-TNF in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed Over 18 Other, Pharmaceutical / Industry EORTC-16041 MOLMED-EORTC-16041, EUDRACT-2004-000950-21, NCT00098943

Objectives

Primary

1. Determine the dose-limiting toxicity and maximum tolerated dose of tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) in patients with advanced solid tumors.
2. Determine the recommended phase II dose of this drug in these patients.

Secondary

1. Determine the mechanism of action of this drug in these patients.
2. Determine response in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Diagnosis of advanced solid tumor not amenable to any clinical improvement by current standard treatments
  • Preferably tumors well known to be very angiogenic (e.g., renal, colon, thyroid, and head and neck cancers)



• No clinical signs of CNS involvement

Prior/Concurrent Therapy:

Biologic therapy

• At least 28 days since prior immunotherapy

Chemotherapy

• At least 28 days since prior chemotherapy and recovered

Endocrine therapy

• At least 28 days since prior hormonal therapy

Radiotherapy

• At least 28 days since prior radiotherapy and recovered
• No prior radiotherapy to > 25% of bone marrow reserve

Surgery

• More than 2 weeks since prior surgery

Other

• No other concurrent anticancer therapy
• No other concurrent investigational agents

Patient Characteristics:

Age

• Over 18

Performance status

• ECOG 0-2

  OR

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and/or ALT < 2.5 times ULN (5 times ULN in the presence of liver metastases)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• Cardiac function normal
• No uncontrolled hypertension
• No condition in which hypovolemia and its consequences (e.g., increased stroke volume, elevated blood pressure) or hemodilution could represent a risk to the patient

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No active or uncontrolled systemic infection
• No other uncontrolled disease, serious illness, or medical condition that would preclude study participation
• No known hypersensitivity/allergic reaction to human albumin preparations or any of the excipients
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

Expected Enrollment

A total of 1-30 patients will be accrued for this study.

Outcomes

Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0

Clinical response as measured by RECIST criteria
Mechanism of action as measured by Dynamic Imaging

Outline

This is an open-label, nonrandomized, dose-escalation, multicenter study.

Patients receive tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) IV over 1 hour on day 1. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 1-6 patients receive escalating doses of NGR-TNF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients receive treatment at the MTD.

Patients are followed every 8 weeks until disease progression or the start of a new anticancer treatment.

Van Laarhoven H, Fiedler W, Desar IM, et al.: Phase I and DCE-MRI evaluation of NGR-TNF, a novel vascular targeting agent, in patients with solid tumors (EORTC 16041). [Abstract] J Clin Oncol 26 (Suppl 15): A-3521, 2008.

Heerschap A, Fiedler W, Marreaud S, et al.: A phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] J Clin Oncol 25 (Suppl 18): A-14074, 2007.

van Herpen C, Fiedler W, Marreaud S, et al.: A biological and pharmacologic phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-B78, 2007.

van Herpen C, Fiedler W, Toma S, et al.: Phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumours (EORTC 16041). [Abstract] European Journal of Cancer Supplements 4 (12): A-366, 113, 2006.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Cornelis Punt, MD, PhD, Study coordinator		Ph: 31-24-361-0353 Email: c.punt@onco.umcn.nl

Registry Information
Official Title		Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients with Solid Tumor
Trial Start Date		2004-09-03
Trial Completion Date		2008-01-31 (estimated)
Registered in ClinicalTrials.gov		NCT00098943
Date Submitted to PDQ		2004-10-05
Information Last Verified		2007-10-07