TNF-Bound Colloidal Gold in Treating Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose of TNF-bound colloidal gold (CYT-6091) []
- Toxicity []
Secondary Outcome Measures
- 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 []
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda | Maryland | United States | 20892-1182 |
| 2 | NCI - Surgery Branch | Bethesda | Maryland | United States | 20892-1201 |
Sponsors and Collaborators
- National Institutes of Health Clinical Center (CC)
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Steven K. Libutti, MD, NCI - Surgery Branch
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 060167
- 06-C-0167
- NCI-P6062
- CYT-6091-06-01
- CDR0000486917
- NCT00328406