NGR-TNF in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Biological: CNGRC peptide-TNF alpha conjugate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: CNGRC peptide-TNF alpha conjugate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response as measured by RECIST criteria |  |  | 
| Mechanism of action as measured by Dynamic Imaging |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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