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Percutaneous Cryotherapy and Aerosolized GM-CSF for Pulmonary Metastases and Primary Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Kidney Cancer, Lung Cancer, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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
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.

Inclusion Criteria


- 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

- 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

- 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

- Inactive history of cancer allowed if the patient has been disease-free for > 2

- 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


- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Immunologic response as measured by ELISPOT assay and flow cytometry

Outcome Description:

CT-guided biopsy & Peritumoral GM-CSF

Outcome Time Frame:

Days 1 & 32

Safety Issue:


Principal Investigator

Peter J. Littrup, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

January 2006

Completion Date:

Related Keywords:

  • Kidney Cancer
  • Lung Cancer
  • Metastatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • lung metastases
  • stage I non-small cell lung cancer
  • stage II non-small cell lung cancer
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • recurrent non-small cell lung cancer
  • recurrent renal cell cancer
  • stage IV renal cell cancer
  • unspecified adult solid tumor, protocol specific
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Lung Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
Sinai-Grace Hospital Detroit, Michigan  48235