NGR-TNF in Treating Patients With Advanced Solid Tumors

Colorectal Cancer Clinical Trial

Official title:

Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients With Solid Tumor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00098943
• Other study ID #: EORTC-16041
• Secondary ID: EORTC-16041MOLME
• Status: Completed
• Phase: Phase 1
• First received: December 8, 2004
• Last updated: September 20, 2012
• Start date: September 2004

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Targeted therapy with tumor necrosis factor combined with a fusion protein may stop the growth of solid tumors by stopping blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of NGR-TNF in treating patients with advanced solid tumors.

Description:

OBJECTIVES:

Primary

• 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.

• Determine the recommended phase II dose of this drug in these patients.

Secondary

• Determine the mechanism of action of this drug in these patients.

• Determine response in patients treated with this drug.

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-2 OR

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3

• Platelet count > 100,000/mm^3

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

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Kidney Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Biological:
• CNGRC peptide-TNF alpha conjugate

Locations

Country	Name	City	State
Germany	University Medical Center Hamburg - Eppendorf	Hamburg
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Germany,  Netherlands, 

References & Publications (5)

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

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.

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.

van Laarhoven HW, Fiedler W, Desar IM, van Asten JJ, Marréaud S, Lacombe D, Govaerts AS, Bogaerts J, Lasch P, Timmer-Bonte JN, Lambiase A, Bordignon C, Punt CJ, Heerschap A, van Herpen CM. Phase I clinical and magnetic resonance imaging study of the vascu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0			Yes
Secondary	Clinical response as measured by RECIST criteria			No
Secondary	Mechanism of action as measured by Dynamic Imaging			No