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: Phase I trial to study the effectiveness of NGR-TNF in treating patients who have advanced solid tumors.

Condition	Treatment or Intervention	Phase
adult solid tumor Endocrine Cancer Gastrointestinal Cancer Head and Neck Cancer kidney and urinary cancer	Drug: CNGRC peptide-tumor necrosis factor alpha conjugate  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: cytokine therapy  Procedure: growth factor antagonist therapy  Procedure: targeted fusion protein therapy  Procedure: tumor necrosis factor therapy	Phase I

Further Study Details: 

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 20 minutes 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

Germany
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany; Recruiting
Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting

Study chairs or principal investigators

Cornelis J. A. Punt, MD, PhD,  University Medical Center Nijmegen   

Study ID Numbers:  CDR0000396507; EORTC-16041; MOLMED-EORTC-16041; EUDRACT-2004-000950-21; NCT00098943
Record last reviewed:  November 2004
Last Updated:  February 4, 2005
Record first received:  December 8, 2004
ClinicalTrials.gov Identifier:  NCT00098943
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08