NGR-TNF in Treating Patients With Advanced Solid Tumors

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.

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