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

NCT ID: NCT00514215

Last Updated: 2020-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2010-03-31

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.

Conditions

Kidney Cancer; Lung Cancer; Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

250 μg, inhaled, two times a day, on days 4-10 and days 36-42

flow cytometry

Intervention Type: OTHER

Days 1 \& 32

immunoenzyme technique

Intervention Type: OTHER

Days 1 \& 32

biopsy

Intervention Type: PROCEDURE

CT guided biopsy on days 1 \& 32

cryosurgery

Intervention Type: PROCEDURE

Days 1 and 32

Interventions

sargramostim

250 μg, inhaled, two times a day, on days 4-10 and days 36-42

Intervention Type: BIOLOGICAL

flow cytometry

Days 1 \& 32

Intervention Type: OTHER

immunoenzyme technique

Days 1 \& 32

Intervention Type: OTHER

biopsy

CT guided biopsy on days 1 \& 32

Intervention Type: PROCEDURE

cryosurgery

Days 1 and 32

Intervention Type: PROCEDURE

Other Intervention Names

GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor); Leukine

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Peter Littrup

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter J. Littrup, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Related Links

http://cancer.gov/clinicaltrials

Clinical trial summary from the National Cancer Institute's PDQ® database

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-C-2795

Identifier Type: -

Identifier Source: secondary_id

WSU-HIC-050304M1(R)F

Identifier Type: -

Identifier Source: secondary_id

CDR0000559667

Identifier Type: -

Identifier Source: org_study_id