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

Phase 2

Completed

Conditions: Kidney Cancer
Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Metastatic Cancer

Interventions: Biological: sargramostim
Other: flow cytometry
Other: immunoenzyme technique
Procedure: biopsy
Procedure: cryosurgery

Registration Number: NCT00514215

Lead Sponsor: Barbara Ann Karmanos Cancer Institute

Brief Summary: 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.

Detailed Description: OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sargramostim, Flow Cytometry, Biopsy. Cryosurgery	flow cytometry	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
Sargramostim, Flow Cytometry, Biopsy. Cryosurgery	immunoenzyme technique	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
Sargramostim, Flow Cytometry, Biopsy. Cryosurgery	sargramostim	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
Sargramostim, Flow Cytometry, Biopsy. Cryosurgery	biopsy	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
Sargramostim, Flow Cytometry, Biopsy. Cryosurgery	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

Primary Outcome Measures

Name	Time	Method
Immunologic Response as Measured by ELISPOT Assay and Flow Cytometry	Days 1 & 32	CT-guided biopsy \& Peritumoral GM-CSF. a CR was defined as involution of the prior tumor and/or ablation site to only a thin, non-enhancing scar within the pulmonary parenchyma on enhanced chest CT. A PR was defined as incomplete resolution of an otherwise thoroughly hypovascular resolving ablation zone which had reached a diameter smaller than the original tumor size. Stable disease (SD) reflects no significant change in size of ablation site and/or overall tumor burden, while the standard definition for progressive disease (PD) remains as evidence of neTw or growing tumors.

Secondary Outcome Measures

Name	Time	Method
Toxicity of Grade 1 or Higher	Days 11, 32, 43, & 63	Number of Participants with Toxicity of Grade 1 or Higher as defined by CTCAE v2
Clinical Response as Measured by CT Criteria	Days 1 & 32	CT-guided biopsy. a CR was defined as involution of the prior tumor and/or ablation site to only a thin, non-enhancing scar within the pulmonary parenchyma on enhanced chest CT. A PR was defined as incomplete resolution of an otherwise thoroughly hypovascular resolving ablation zone which had reached a diameter smaller than the original tumor size. Stable disease (SD) reflects no significant change in size of ablation site and/or overall tumor burden, while the standard definition for progressive disease (PD) remains as evidence of neTw or growing tumors.
Immune Function and Cancer-specific Response	Days 1 & 63	Number of Participants with CT-guided biopsy \& Peritumoral GM-CSF. The number of IFNγ secreting T-cells was measured by a direct EliSpots at 10:1 E:T ratio to define the kinetics of the CTL responses from pre-CI to day 63 post CI.