TNF-Bound Colloidal Gold in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as TNF-bound colloidal gold, may stimulate the immune system in different ways and stop tumor cells from growing. PURPOSE: This phase I trial is studying the side effects and best dose of TNF-bound colloidal gold in treating patients with advanced solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of TNF-bound colloidal gold (CYT-6091) in patients with advanced solid tumors. Determine the toxicities of CYT-6091 in these patients. Secondary Determine the pharmacokinetics of CYT-6091 in these patients. Evaluate biopsy samples of tumor and adjoining normal tissue for levels of CYT-6091. Determine if antitumor effects of CYT-6091 occur in these patients. OUTLINE: This is an open-label, sequential cohort, dose-escalation study. Patients receive TNF-bound colloidal gold (CYT-6091) IV on days 1 and 15 (course 1). Approximately 4-6 weeks later, patients are re-staged and responding patients may receive another course of therapy. Patients may receive up to 3 re-treatment courses. Cohorts of 3-6 patients receive escalating doses of CYT-6091 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 6 patients experience dose-limiting toxicity. Blood samples are collected at baseline and periodically during the first course of therapy for pharmacokinetic and pharmacodynamic analyses. After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for the next year, and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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A Phase I Trial of TNF-Bound Colloidal Gold (CYT-6091) by Intravenous Administration in Subjects With Advanced Solid Organ Malignancies

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: colloidal gold-bound tumor necrosis factor
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed solid tumor Advanced and/or metastatic disease Unresponsive to conventional therapy (i.e., disease progressed while receiving any known standard curative or palliative therapy) OR previously untreated tumor for which no standard treatment exists Measurable or evaluable metastatic disease No lymphoma or other hematologic malignancy No known brain metastases Previously treated brain metastases with no evidence of recurrence allowed PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 2.0 mg/dL Bilirubin ≤ 2.5 mg/dL ALT and AST ≤ 1.5 times upper limit of normal (ULN) (3 times ULN if liver metastases are present) Alkaline phosphatase ≤ 1.5 times ULN (3 times ULN if liver metastases are present) Prothrombin time ≤ 1.5 times ULN Hemoglobin ≥ 10.0 g/dL (transfusion allowed) LVEF ≥ 45% by echocardiogram or thallium stress test for patients > 50 years of age or history of cardiovascular disease FEV_1 and DLCO > 30% of predicted for patients with a history of pulmonary disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active bacterial or viral infection with systemic manifestations (e.g., fever, symptoms, leukocytosis) Localized chronic infections, such as mild acne or tinea pedis allowed No acute or chronic viral hepatitis No known bleeding disorder No other concurrent life-threatening illness, including any of the following: Unstable angina Severe oxygen-dependent chronic obstructive pulmonary disease End-stage liver disease No known active renal disease or renal insufficiency as evidenced by serum creatinine > 2.0 mg/dL No HIV positivity PRIOR CONCURRENT THERAPY: Recovered from prior therapy More than 3 weeks since prior biological or cytotoxic agents (6 weeks for nitrosoureas) No known requirment for palliative treatment No concurrent surgery No other concurrent anticancer therapy

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: colloidal gold-bound tumor necrosis factor|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of TNF-bound colloidal gold (CYT-6091) |  |  | 
| Toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of CYT-6091 |  |  | 
| Measurements of CYT-6091 in tumor biopsies |  |  | 
| Tumor biopsy histology and gene expression after treatment |  |  | 
| Immunogenicity of CYT-6091 |  |  | 
| Electron microscopy of biopsy to determine presence of colloidal gold |  |  | 
| Response of target and nontarget lesions |  |  | 
| Overall response |  |  | 
| Duration of response |  |  | 
| Duration of stable disease |  |  | 

 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