Gold Sodium Thiomalate in Treating Patients With Advanced Non-Small Cell Lung Cancer

Mayo Clinic

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

Treatments: Other: pharmacological study; Other: mass spectrometry; Other: fluorine F 18 fluorothymidine; Genetic: gene expression analysis; Drug: gold sodium thiomalate

Study type: Interventional

Funder types: Other

Identifiers

NCT00575393

06-003532 (Other Identifier)

MC0622 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Gold sodium thiomalate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of gold sodium thiomalate in treating patients with advanced non-small cell lung cancer.

Full description

OBJECTIVES:

• To determine the maximum tolerated dose of gold sodium thiomalate in patients with advanced non-small cell lung cancer.
• To describe the toxicities associated with this treatment.
• To describe any preliminary evidence of biologic activity.
• To further assess the correlation between PKCι expression and the antitumor effects of gold sodium thiomalate.
• To study the association of clinical (toxicity and/or tumor response or activity) with pharmacokinetic/pharmacodynamic parameters.
• To describe anti-proliferative activity of gold sodium thiomalate through 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.

OUTLINE: This is a dose-escalation study of gold sodium thiomalate.

Patients receive gold sodium thiomalate intramuscularly on days 1, 8, 15 and 22. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive gold sodium thiomalate once every 4 weeks until a total cumulative dose of 1 gram is delivered.

Blood samples are collected at baseline and prior to therapy in weeks 3, 5, 7, 9, and 11. Samples are analyzed by mass spectometry for pharmacokinetics. Paraffin-embedded tumor tissue samples are analyzed for PKC_l expression and antitumor activity. Antiproliferative effects of gold sodium thiomalate are analyzed by 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.

Enrollment: 17 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced non-small cell lung cancer
• No known standard therapy for disease that is potentially curative or definitely capable of extending life expectancy
• No symptomatic or worsening CNS metastases despite optimal therapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if liver involvement)
• Creatinine ≤ 1.2 times ULN
• Hemoglobin ≥ 9.0 g/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must be willing to provide blood and tissue samples
• No uncontrolled infection
• No New York Heart Association class III or IV heart disease
• No known allergy to gold sodium thiomalate

PRIOR CONCURRENT THERAPY:

• Recovered from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
• No prior chemotherapy within the past 3 weeks
• No prior mitomycin C or nitrosoureas within the past 6 weeks
• No prior immunotherapy within the past 3 weeks
• No prior biologic therapy within the past 3 weeks
• No prior radiotherapy within the past 3 weeks
• No prior radiotherapy to > 25% of bone marrow
• No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation)
• No concurrent prophylactic colony stimulating factors