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

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: pharmacological study; Biological: colloidal gold-bound tumor necrosis factor

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Bethesda, Maryland, United States, 20892-1201
      • NCI - Surgery Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Duration of response
Duration of stable disease
Overall response
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

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 26, 2006
• First Submitted That Met QC Criteria: July 26, 2006
• First Posted (Estimate): July 27, 2006

Study Record Updates

• Last Update Posted (Estimate): March 15, 2012
• Last Update Submitted That Met QC Criteria: March 14, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Other Study ID Numbers: 060167; 06-C-0167; NCI-P6062; CYT-6091-06-01; CDR0000486917