A Phase I Dose Escalation Study of the PKC Inhibitor, Aurothiomalate (ATM) in Patients With Advanced Non-Small Cell Lung Cancer
18 Years
N/A
Both
Lung Cancer
Trial Information
A Phase I Dose Escalation Study of the PKC Inhibitor, Aurothiomalate (ATM) in Patients With Advanced Non-Small Cell Lung Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose
Safety Issue:
Yes
Principal Investigator
Julian Molina, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
Unspecified
Study ID:
CDR0000579311
NCT ID:
NCT00575393
Start Date:
January 2007
Completion Date:
Related Keywords:
- Lung Cancer
- stage IIIB non-small cell lung cancer
- stage IV non-small cell lung cancer
- recurrent non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Mayo Clinic Scottsdale | Scottsdale, Arizona 85259 |
| Mayo Clinic - Jacksonville | Jacksonville, Florida 32224 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
