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.

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.

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