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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Peter Littrup, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00514215
First received: August 8, 2007
Last updated: November 18, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Lung Cancer
Metastatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Biological: sargramostim
Other: flow cytometry
Other: immunoenzyme technique
Procedure: biopsy
Procedure: cryosurgery
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Percutaneous Cryotherapy and Aerosolized GM-CSF for Pulmonary Metastases and Primary Lung Cancer

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Immunologic response as measured by ELISPOT assay and flow cytometry [ Time Frame: Days 1 & 32 ] [ Designated as safety issue: No ]
    CT-guided biopsy & Peritumoral GM-CSF


Secondary Outcome Measures:
  • Clinical response as measured by CT criteria [ Time Frame: Days 1 & 32 ] [ Designated as safety issue: No ]
    CT-guided biopsy

  • Toxicity [ Time Frame: Days 11, 32, 43, & 63 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    CT-guided biopsy & Peritumoral GM-CSF


Enrollment: 8
Study Start Date: January 2006
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514215

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Peter J. Littrup, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Peter Littrup, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00514215     History of Changes
Other Study ID Numbers: CDR0000559667, P30CA022453, WSU-C-2795, WSU-HIC-050304M1(R)F
Study First Received: August 8, 2007
Last Updated: November 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
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

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Lung Neoplasms
Neoplasm Metastasis
Adenocarcinoma
Carcinoma
Kidney Diseases
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on October 20, 2014