Clinical trial NCT00098943: NGR-TNF in Treating Patients With Advanced Solid Tumors
Official title: Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients With Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Head and Neck Cancer
Kidney Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
stage IV renal cell cancer
recurrent renal cell cancer
stage IV colon cancer
recurrent colon cancer
anaplastic thyroid cancer
insular thyroid cancer
thyroid gland medullary carcinoma
stage IV follicular thyroid cancer
stage IV papillary thyroid cancer
recurrent thyroid cancer
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent verrucous carcinoma of the larynx
recurrent verrucous carcinoma of the oral cavity
stage IV verrucous carcinoma of the oral cavity
stage IV verrucous carcinoma of the larynx
recurrent adenoid cystic carcinoma of the oral cavity
stage IV adenoid cystic carcinoma of the oral cavity
recurrent basal cell carcinoma of the lip
stage IV basal cell carcinoma of the lip
recurrent mucoepidermoid carcinoma of the oral cavity
stage IV mucoepidermoid carcinoma of the oral cavity
recurrent lymphoepithelioma of the nasopharynx
recurrent lymphoepithelioma of the oropharynx
stage IV lymphoepithelioma of the nasopharynx
stage IV lymphoepithelioma of the oropharynx
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
metastatic parathyroid cancer
recurrent parathyroid cancer
recurrent salivary gland cancer
stage IV salivary gland cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-12-09
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

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

Primary outcomes:
measure: Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0
Secondary outcomes:
measure: Clinical response as measured by RECIST criteria
measure: Mechanism of action as measured by Dynamic Imaging
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
Study officials:
affiliation: Universitair Medisch Centrum St. Radboud - Nijmegen
name: Cornelis J. A. Punt, MD, PhD
role: STUDY_CHAIR
References:
citation: van Laarhoven HW, Fiedler W, Desar IM, van Asten JJ, Marreaud 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 vascular agent NGR-hTNF in patients with advanced cancers (European Organization for Research and Treatment of Cancer Study 16041). Clin Cancer Res. 2010 Feb 15;16(4):1315-23. doi: 10.1158/1078-0432.CCR-09-1621. Epub 2010 Feb 9.
citation: 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.
citation: 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.
citation: 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.
citation: 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.