Cryotherapy and GM-CSF in Treating Patients With Lung Metastases or Primary Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00514215
Recruitment Status : Completed
First Posted : August 9, 2007
Results First Posted : February 23, 2015
Last Update Posted : February 23, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Peter Littrup, Barbara Ann Karmanos Cancer Institute

August 8, 2007
August 9, 2007
February 9, 2015
February 23, 2015
February 23, 2015
January 2006
March 2010   (Final data collection date for primary outcome measure)
Immunologic Response as Measured by ELISPOT Assay and Flow Cytometry [ Time Frame: Days 1 & 32 ]
CT-guided biopsy & Peritumoral GM-CSF
Immunologic Response as Measured by ELISPOT Assay and Flow Cytometry
Complete list of historical versions of study NCT00514215 on Archive Site
  • Clinical Response as Measured by CT Criteria [ Time Frame: Days 1 & 32 ]
    CT-guided biopsy
  • Toxicity [ Time Frame: Days 11, 32, 43, & 63 ]
    CBC, sodium, potassium, BUN, serum creatinine, calcium, glucose, SGOT, Alk Phos, bilirubin, Electrolytes, Albumin (Alb), Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), Total bilirubin (TBIL), Direct bilirubin (Conjugated Bilirubin), Gamma glutamyl transpeptidase (GGT)
  • Immune Function and Cancer-specific Response [ Time Frame: Days 1 & 32 ]
    CT-guided biopsy & Peritumoral GM-CSF
  • Clinical Response as Measured by CT Criteria
  • Toxicity
  • Immune Function and Cancer-specific Response
Not Provided
Not Provided
Cryotherapy and GM-CSF in Treating Patients With Lung Metastases or Primary Lung Cancer
Percutaneous Cryotherapy and Aerosolized GM-CSF for Pulmonary Metastases and Primary Lung Cancer

RATIONALE: Cryotherapy kills tumor cells by freezing them. Giving an injection of GM-CSF before cryotherapy and inhaling GM-CSF after cryotherapy may interfere with the growth of tumor cells and shrink the tumor. Giving cryotherapy together with GM-CSF may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cryotherapy together with GM-CSF works in treating patients with lung metastases or 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 regimen.
  • 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 TGF-β1-secreting cells.


  • 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.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Kidney Cancer
  • Lung Cancer
  • Metastatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Biological: sargramostim
    250 μg, inhaled, two times a day, on days 4-10 and days 36-42
    Other Names:
    • GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor)
    • Leukine
  • Other: flow cytometry
    Days 1 & 32
  • Other: immunoenzyme technique
    Days 1 & 32
  • Procedure: biopsy
    CT guided biopsy on days 1 & 32
  • Procedure: cryosurgery
    Days 1 and 32
Experimental: Sargramostim, Flow Cytometry, Biopsy. Cryosurgery
Sargramostim-250 μg, inhaled, two times a day, on days 4-10 and days 36-42 Flow cytometry-Days 1 & 32 Immunoenzyme technique-Days 1 & 32 CT guided biopsy-Days 1 & 32 Cryosurgery-Days 1 and 32
  • Biological: sargramostim
  • Other: flow cytometry
  • Other: immunoenzyme technique
  • Procedure: biopsy
  • Procedure: cryosurgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
March 2010
March 2010   (Final data collection date for primary outcome measure)


  • Histologically confirmed diagnosis of 1 of the following:

    • Primary non-small cell lung cancer (NSCLC)

      • Any stage nonoperative NSCLC or patient refuses surgery
    • Any cancer with pulmonary metastatic disease (including renal cell cancer)

      • Stage IV disease (any T, any N, M1)
  • Must have 1-10 pulmonary or mediastinal masses meeting the following criteria:

    • At least 1 mass is appropriate for 2 sessions of core biopsy and cryotherapy with relatively easy access/low risk in nonoperative patients (or those refusing surgery)
    • The two dominant masses are defined as either the largest and/or those that may cause imminent morbidity from continued local progression, thereby potentially benefiting from thoracic cryotherapy alone
    • Optimal tumor size > 1.0 cm

      • Dominant masses up to 6 cm in diameter may be considered if thorough cryotherapy coverage can be anticipated with minimal additional treatment morbidity
  • Measurable disease, defined as tridimensional measurements of up to 6 different pulmonary or mediastinal masses ≥ 0.5 cm by CT scan
  • No active pleural effusion that could be related to respiratory infection or requires further work-up
  • No untreated and/or unstable brain metastases


  • Karnofsky performance status 70-100%
  • Life expectancy ≥ 12 weeks
  • Granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 50,000/mm³
  • INR < 1.5 (i.e., normal PT/PTT)
  • Hemoglobin ≥ 8.0 g/dL
  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • Satisfactory pulmonary function test as determined by supervising oncologist, thoracic surgeon, or pulmonologist
  • Not pregnant or lactating
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix

    • Inactive history of cancer allowed if the patient has been disease-free for > 2 years
  • No serious medical or psychiatric illnesses that would preclude informed consent or limit survival to < 12 wks
  • No uncontrollable cough or inability to lie flat
  • No New York Heart Association class III or IV heart disease
  • No known immunodeficiency state
  • No uncontrolled infection
  • No uncontrolled coagulopathy or bleeding diathesis
  • No advance directive that would prevent the investigator from treating the participant in the event of a complication occurring during or after the procedure
  • No medical contraindication or potential problem that would preclude protocol compliance


  • More than 4 weeks since prior biologic therapy
  • More than 4 weeks since prior immunotherapy
  • More than 4 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 4 weeks since prior radiotherapy
  • More than 2 weeks since prior corticosteroids
  • More than 1 week since prior parenteral antibiotics
  • At least 1 week since prior aspirin or aspirin-like medications
  • At least 3 days since prior warfarin, clopidogrel bisulfate, or similar compounds
  • No concurrent GM-CSF other than study drug
  • No concurrent G-CSF
  • No concurrent radiotherapy
  • No concurrent glucocorticosteroids
  • No concurrent parenteral antibiotics
  • No concurrent immunosuppressive agents
  • No concurrent drugs that cause bleeding tendencies
  • No other concurrent biologic therapy, immunotherapy, radiotherapy, or chemotherapy
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
P30CA022453 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Peter Littrup, Barbara Ann Karmanos Cancer Institute
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Study Chair: Peter J. Littrup, MD Barbara Ann Karmanos Cancer Institute
Barbara Ann Karmanos Cancer Institute
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP