NGR-TNF in Treating Patients With Advanced Solid Tumors

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Kidney Cancer

Head and Neck Cancer

Colorectal Cancer

Treatments

Biological: CNGRC peptide-TNF alpha conjugate

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00098943

EORTC-16041

MOLMED-EORTC-16041

EUDRACT-2004-000950-21

Details and patient eligibility

About

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.

Full 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.

Enrollment

70 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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