Percutaneous Cryotherapy and Aerosolized GM-CSF for Pulmonary Metastases and Primary Lung Cancer
- Determine whether percutaneous cryotherapy in combination with aerosolized sargramostim
(GM-CSF) has any demonstrable immunologic effect in patients with pulmonary metastases
or primary lung cancer.
- Determine whether any systemic immune response is detectable by the combination of
cryotherapy as the antigen presentation source and GM-CSF as the immunologic adjuvant.
- Determine whether low morbidities will be maintained in patients treated with this
- Determine whether effective immunization is associated with a drop in CD4+, CD25+,
LTP(TGF-β1)+, Tr cells as measured by flow cytometry or ELISPOT assay for
- Determine clinical response (i.e., tumor control in the dominant masses undergoing
cryotherapy or in other metastatic sites) as measured by CT criteria.
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients undergo CT-guided core biopsy of a dominant lung mass and placement of at
least 2 cryoprobes. Prior to initiating the freeze, patients receive an interstitial
injection of sargramostim (GM-CSF) near the tumor. Patients then undergo percutaneous
cryotherapy over 2 hours utilizing a freeze-thaw-freeze cycle. Beginning within 3 days of
cryotherapy, patients receive aerosolized GM-CSF twice daily for 1 week. Beginning on day
32, patients may elect to undergo a second course of treatment as described above in the
absence of disease progression or unacceptable toxicity.
Patients undergo blood and tumor tissue collection at baseline and periodically during study
for immunological correlative studies. Peripheral blood mononuclear cells isolated from
blood samples are analyzed for antigen-specific CD4-positive or CD8-positive T-cell response
by flow cytometry or by TGF-β1 ELISPOT assay to measure TGF-β1- secreting cells. Tumor cell
lysates extracted from tumor samples are pulsed with autologous dendritic cells and analyzed
by ELISPOT assay to measure T-cell reactivity in tumor specimens.
After completion of study therapy, patients are followed at 6 and 12 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Immunologic response as measured by ELISPOT assay and flow cytometry
CT-guided biopsy & Peritumoral GM-CSF
Days 1 & 32
Peter J. Littrup, MD
Barbara Ann Karmanos Cancer Institute
United States: Food and Drug Administration
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|
|Sinai-Grace Hospital||Detroit, Michigan 48235|