Clinical trial NCT00356980: TNF-Bound Colloidal Gold in Treating Patients With Advanced Solid Tumors
Official title: A Phase I Trial of TNF-Bound Colloidal Gold (CYT-6091) by Intravenous Administration in Subjects With Advanced Solid Organ Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-07-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose of TNF-bound colloidal gold (CYT-6091)
measure: Toxicity
Secondary outcomes:
measure: Pharmacokinetic profile of CYT-6091
measure: Measurements of CYT-6091 in tumor biopsies
measure: Tumor biopsy histology and gene expression after treatment
measure: Immunogenicity of CYT-6091
measure: Electron microscopy of biopsy to determine presence of colloidal gold
measure: Response of target and nontarget lesions
measure: Overall response
measure: Duration of response
measure: Duration of stable disease
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
state: Maryland
city: Bethesda
country: United States
facility: NCI - Surgery Branch
state: Maryland
Study officials:
affiliation: NCI - Surgery Branch
name: Steven K. Libutti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Libutti SK, Paciotti GF, Byrnes AA, Alexander HR Jr, Gannon WE, Walker M, Seidel GD, Yuldasheva N, Tamarkin L. Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine. Clin Cancer Res. 2010 Dec 15;16(24):6139-49. doi: 10.1158/1078-0432.CCR-10-0978. Epub 2010 Sep 27.