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Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma

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ClinicalTrials.gov Identifier: NCT00066365
Recruitment Status : Completed
First Posted : August 7, 2003
Results First Posted : March 30, 2015
Last Update Posted : March 30, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Metastatic Cancer
Sarcoma
Interventions Biological: sargramostim
Procedure: conventional surgery
Enrollment 49
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Period Title: Overall Study
Started 31 18
Completed 8 4
Not Completed 23 14
Reason Not Completed
Adverse Event             1             0
Lack of Efficacy             15             12
Physician Decision             1             0
No viable tumor after 1 cycle of therapy             2             0
Ineligible             4             2
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy Total
Hide Arm/Group Description

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Total of all reporting groups
Overall Number of Baseline Participants 31 18 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 18 participants 49 participants
<=18 years
25
  80.6%
14
  77.8%
39
  79.6%
Between 18 and 65 years
6
  19.4%
4
  22.2%
10
  20.4%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 31 participants 18 participants 49 participants
16
(7 to 29)
17
(14 to 20)
16
(7 to 29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 18 participants 49 participants
Female
15
  48.4%
5
  27.8%
20
  40.8%
Male
16
  51.6%
13
  72.2%
29
  59.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 18 participants 49 participants
Hispanic or Latino
2
   6.5%
1
   5.6%
3
   6.1%
Not Hispanic or Latino
29
  93.5%
15
  83.3%
44
  89.8%
Unknown or Not Reported
0
   0.0%
2
  11.1%
2
   4.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 18 participants 49 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   3.2%
0
   0.0%
1
   2.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  22.6%
0
   0.0%
7
  14.3%
White
22
  71.0%
16
  88.9%
38
  77.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.2%
2
  11.1%
3
   6.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 31 participants 18 participants 49 participants
United States 30 18 48
Canada 1 0 1
1.Primary Outcome
Title Status of FAS Ligand in Pre-chemotherapy Sample
Hide Description FAS ligand (FASL) is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. The Cluster of Differentiation 1a (CD1a) status is measured in Immunohistochemistry (IHC) categories.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who were enrolled in the unilateral recurrence group do not contribute to the assessment of any “Pre Chemotherapy” analysis. Such patients only had tissue for assessment after the first thoracotomy which was planned for 22 days after the start of sargramostim treatment. 14 patients were evaluated for this primary outcome measure.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 0 14
Measure Type: Number
Unit of Measure: participants
IHC Category 0 7
IHC Category 1 5
IHC Category 2 1
IHC Category 3 1
2.Primary Outcome
Title Presence of FAS in Pre-chemotherapy Sample
Hide Description FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who were enrolled in Group 1 (unilateral recurrence) do not contribute to the assessment of any “Pre Chemotherapy” analysis. Such patients only had tissue for assessment after the first thoracotomy which was planned for 22 days after the start of sargramostim treatment.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 0 14
Measure Type: Number
Unit of Measure: participants
IHC Category 0 5
IHC Category 1 5
IHC Category 2 2
IHC Category 3 2
3.Primary Outcome
Title FAS Ligand in Post Chemotherapy Sample
Hide Description FAS ligand or FASL is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. The presence is measured in Immunohistochemistry (IHC) categories.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
22 patients from the unilateral recurrence group and 13 patients from the bilateral recurrence group were evaluated for this outcome measure.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 22 13
Measure Type: Number
Unit of Measure: participants
IHC Category 0 16 7
IHC Category 1 4 2
IHC Category 2 1 2
IHC Category 3 1 2
4.Primary Outcome
Title FAS Status in Post Chemotherapy Sample
Hide Description FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
22 patients from the unilateral recurrence group and 13 patients from the bilateral recurrence group were evaluated for this outcome measure.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 22 13
Measure Type: Number
Unit of Measure: participants
IHC Category 0 14 5
IHC Category 1 4 4
IHC Category 2 1 0
IHC Category 3 3 4
5.Primary Outcome
Title CD1a Status in Pre Chemotherapy Sample
Hide Description CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in the unilateral recurrence group do not contribute to the assessment of any “Pre Chemotherapy” analysis. Such patients only had tissue for assessment after the first thoracotomy which was planned for 22 days after the start of sargramostim treatment. 7 patients were evaluated from the bilateral recurrence group.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 0 7
Measure Type: Number
Unit of Measure: participants
Negative 5
Focally Positive 2
6.Primary Outcome
Title CD1a Status in Post Chemotherapy Sample
Hide Description CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
20 patients were evaluated for this outcome measure from the unilateral group and 7 patients were evaluated from the bilateral group.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 20 7
Measure Type: Number
Unit of Measure: participants
Negative 8 5
Focally Positive 12 2
7.Primary Outcome
Title S100 Status in Pre Chemotherapy Sample
Hide Description The S-100 proteins are a family of low-molecular-weight proteins characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand type") conformation.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in the unilateral recurrence group do not contribute to the assessment of any “Pre Chemotherapy” analysis. Such patients only had tissue for assessment after the first thoracotomy which was planned for 22 days after the start of sargramostim treatment. 7 patients were evaluated from the bilateral recurrence group.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 0 7
Measure Type: Number
Unit of Measure: participants
Negative 4
Focally Positive 3
8.Primary Outcome
Title S100 Status in Post Chemotherapy Sample
Hide Description The S-100 proteins are a family of low-molecular-weight proteins characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand type") conformation.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
20 patients from the unilateral recurrence group and 10 patients from the bilateral recurrence group were evaluated for this outcome measure.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 20 10
Measure Type: Number
Unit of Measure: participants
Negative 17 9
Focally Positive 3 1
9.Primary Outcome
Title Clusterin Status in Pre Chemotherapy Sample
Hide Description The protein encoded by this gene can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders.
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
Patients enrolled in the unilateral recurrence group do not contribute to the assessment of any “Pre Chemotherapy” analysis. Such patients only had tissue for assessment after the first thoracotomy which was planned for 22 days after the start of sargramostim treatment. 7 patients were measured from the bilateral recurrence group.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 0 7
Measure Type: Number
Unit of Measure: participants
Negative 5
Focally Positive 2
10.Primary Outcome
Title Clusterin Status in Post Chemotherapy Sample
Hide Description [Not Specified]
Time Frame 29 days after start of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was evaluated in 30 patients, 20 patients in the unilateral recurrence group and 10 patients in bilateral recurrence group.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 20 10
Measure Type: Number
Unit of Measure: participants
Negative 17 7
Focally Positive 3 3
11.Primary Outcome
Title Event Free Survival (EFS)
Hide Description EFS defined as the time from enrollment on the study until disease progression, occurrence of a second malignant neoplasm (SMN), death or last contact, whichever comes first. Disease progression, occurrence of a SMN or death will be considered an analytic even. In all other cases, the patient will be considered censored at last contact.
Time Frame Time of enrollment to Event or 5 years from enrollment, whichever occurs first
Hide Outcome Measure Data
Hide Analysis Population Description
There were 4 ineligible unilateral patients and 2 ineligible bilateral patients not included in this analysis.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 27 16
Median (95% Confidence Interval)
Unit of Measure: years
.57
(.31 to .68)
.33
(.19 to .49)
12.Primary Outcome
Title Feasibility Success
Hide Description Feasibility success defined as received 21 days of protocol therapy, did not experience grade III or grade IV toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 3 and rendered surgically free of disease in the lungs.
Time Frame Enrollment through 21 days of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was calculated for eligible patients only. This yields 27 patients for assessment of this measure in Group 1 and 16 patients for assessment of this measure in Group 2.
Arm/Group Title Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
Hide Arm/Group Description:

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo unilateral thoracotomy. Patients receive initial inhalation therapy inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

sargramostim: given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery: thoracotomy

Overall Number of Participants Analyzed 27 16
Measure Type: Number
Unit of Measure: participants
Yes 24 16
No 3 0
Time Frame [Not Specified]
Adverse Event Reporting Description SAE field contains NCI Common Toxicity Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. AE counts only based on eligible patients
 
Arm/Group Title Group 1 (Unilateral Recurrence) Group 2 (Bilateral Recurrence)
Hide Arm/Group Description

(See Detailed Description and Interventions for drugs, dosages, delivery method and frequency.)

sargramostim: given by inhalation

conventional surgery: thoracotomy

(See Detailed Description and Interventions for drugs, dosages, delivery method and frequency.)

sargramostim: given by inhalation

conventional surgery: thoracotomy

All-Cause Mortality
Group 1 (Unilateral Recurrence) Group 2 (Bilateral Recurrence)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 (Unilateral Recurrence) Group 2 (Bilateral Recurrence)
Affected / at Risk (%) Affected / at Risk (%)
Total   4/27 (14.81%)   0/16 (0.00%) 
Cardiac disorders     
Left ventricular systolic dysfunction  1/27 (3.70%)  0/16 (0.00%) 
Injury, poisoning and procedural complications     
Postoperative hemorrhage  1/27 (3.70%)  0/16 (0.00%) 
Investigations     
Alanine aminotransferase increased  1/27 (3.70%)  0/16 (0.00%) 
Aspartate aminotransferase increased  1/27 (3.70%)  0/16 (0.00%) 
Creatinine increased  1/27 (3.70%)  0/16 (0.00%) 
Forced expiratory volume decreased  1/27 (3.70%)  0/16 (0.00%) 
Metabolism and nutrition disorders     
Hypocalcemia  1/27 (3.70%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1/27 (3.70%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders - Other  1/27 (3.70%)  0/16 (0.00%) 
Vascular disorders     
Hypotension  1/27 (3.70%)  0/16 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 (Unilateral Recurrence) Group 2 (Bilateral Recurrence)
Affected / at Risk (%) Affected / at Risk (%)
Total   8/27 (29.63%)   4/16 (25.00%) 
Blood and lymphatic system disorders     
Anemia  1/27 (3.70%)  0/16 (0.00%) 
Blood and lymphatic system disorders - Other  1/27 (3.70%)  0/16 (0.00%) 
General disorders     
Non-cardiac chest pain  3/27 (11.11%)  0/16 (0.00%) 
Pain  1/27 (3.70%)  0/16 (0.00%) 
Infections and infestations     
Infections and infestations - Other  1/27 (3.70%)  0/16 (0.00%) 
Injury, poisoning and procedural complications     
Fracture  1/27 (3.70%)  0/16 (0.00%) 
Investigations     
Forced expiratory volume decreased  0/27 (0.00%)  3/16 (18.75%) 
Neutrophil count decreased  1/27 (3.70%)  0/16 (0.00%) 
Platelet count decreased  1/27 (3.70%)  0/16 (0.00%) 
Vital capacity abnormal  0/27 (0.00%)  2/16 (12.50%) 
White blood cell decreased  1/27 (3.70%)  0/16 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycemia  1/27 (3.70%)  0/16 (0.00%) 
Hypocalcemia  1/27 (3.70%)  0/16 (0.00%) 
Hypoglycemia  1/27 (3.70%)  0/16 (0.00%) 
Hypokalemia  1/27 (3.70%)  0/16 (0.00%) 
Hyponatremia  1/27 (3.70%)  0/16 (0.00%) 
Hypophosphatemia  1/27 (3.70%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders     
Neck pain  1/27 (3.70%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1/27 (3.70%)  0/16 (0.00%) 
Bronchospasm  1/27 (3.70%)  0/16 (0.00%) 
Cough  2/27 (7.41%)  0/16 (0.00%) 
Dyspnea  2/27 (7.41%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders - Other  1/27 (3.70%)  0/16 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1/27 (3.70%)  0/16 (0.00%) 
Vascular disorders     
Thromboembolic event  0/27 (0.00%)  1/16 (6.25%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00066365     History of Changes
Other Study ID Numbers: AOST0221
CDR0000315540 ( Other Identifier: Clinical Trials.gov )
COG-AOST0221 ( Other Identifier: Children's Oncology Group )
NCI-2012-02543 ( Other Identifier: NCI )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: August 6, 2003
First Posted: August 7, 2003
Results First Submitted: February 11, 2015
Results First Posted: March 30, 2015
Last Update Posted: March 30, 2015