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

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00066365
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 49
• Locations: 93
• Arms: 2
• Duration (Months): 113
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Inhaling aerosolized sargramostim before and after surgery may interfere with the growth of tumor cells and shrink the tumor so that it can be removed during surgery. Sargramostim may then kill any tumor cells remaining after surgery. This may be an effective treatment for osteosarcoma that has spread to the lung.

PURPOSE: This phase II trial is studying how well inhaled sargramostim works in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cancer; Sarcoma	Biological: sargramostim; Procedure: conventional surgery	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Assess the histological findings from patients with first pulmonary recurrence of osteosarcoma who undergo resection of pulmonary metastases after treatment with 2 courses of aerosolized sargramostim (GM-CSF).

• Determine the event-free survival of patients treated with this drug.

• Determine whether the maximum tolerated dose in the trial of inhaled GM-CSF in adult patients with melanoma is tolerable in pediatric patients.

Secondary

• Determine the effect of specific thoracic surgical management on outcome in patients treated with this drug.

OUTLINE: This is a multicenter, dose escalation study. Patients are assigned to 1 of 2 groups according to the extent of pulmonary recurrence (unilateral or bilateral).

• Group I (unilateral recurrence):

• Initial inhalation therapy: Patients receive inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses.

• Thoracotomy: Patients undergo thoracotomy on day 22.

• Post-thoracotomy inhalation therapy: Beginning on day 29, or as soon as possible thereafter, patients resume inhalation therapy as above for up to 12 additional courses.

• Group II (bilateral recurrence): Patients may be enrolled on study either before or after the first thoracotomy.

• First thoracotomy: Patients undergo unilateral thoracotomy.

• Initial inhalation therapy: Patients receive 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.

• Contralateral thoracotomy: Patients undergo contralateral thoracotomy on day 22.

• Post-thoracotomy inhalation therapy: Beginning on day 29, or as soon as possible, patients resume inhalation therapy as above for up to 12 additional courses.

Treatment in both groups 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.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 1.6-2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Aerosolized GM-CSF (NSC# 613795, IND# 11042) in Patients With First Pulmonary Recurrence of Osteosarcoma
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 (unilateral recurrence) - Sargramostim and thoractomy 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.	Biological: sargramostim; given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.; Other Names: aerosol sargramostim inhaled GM-CSF Granulocyte Macrophage Colony Stimulating Factor rhu GM-CSF rGM-CSF GM-CSF Prokine® Leukine® Interberin® NSC#613795 ; Procedure: conventional surgery; thoracotomy
Experimental: Group 2 (bilateral recurrence) - Sargramostim and thoractomy Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo surgical procedure 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 surgical procedure 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.	Biological: sargramostim; given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.; Other Names: aerosol sargramostim inhaled GM-CSF Granulocyte Macrophage Colony Stimulating Factor rhu GM-CSF rGM-CSF GM-CSF Prokine® Leukine® Interberin® NSC#613795 ; Procedure: conventional surgery; thoracotomy

Outcome Measures

Primary Outcome Measures

1. Status of FAS Ligand in Pre-chemotherapy Sample [29 days after start of protocol therapy]

   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.

2. Presence of FAS in Pre-chemotherapy Sample [29 days after start of protocol therapy]

   FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.

3. FAS Ligand in Post Chemotherapy Sample [29 days after start of protocol therapy]

   FAS ligand or FASL is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. The presence is measured in Immunohistochemistry (IHC) categories.

4. FAS Status in Post Chemotherapy Sample [29 days after start of protocol therapy]

   FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.

5. CD1a Status in Pre Chemotherapy Sample [29 days after start of protocol therapy]

   CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.

6. CD1a Status in Post Chemotherapy Sample [29 days after start of protocol therapy]

   CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.

7. S100 Status in Pre Chemotherapy Sample [29 days after start of protocol therapy]

   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.

8. S100 Status in Post Chemotherapy Sample [29 days after start of protocol therapy]

   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.

9. Clusterin Status in Pre Chemotherapy Sample [29 days after start of protocol therapy]

   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.

10. Clusterin Status in Post Chemotherapy Sample [29 days after start of protocol therapy]

11. Event Free Survival (EFS) [Time of enrollment to Event or 5 years from enrollment, whichever occurs first]

    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.

12. Feasibility Success [Enrollment through 21 days of protocol therapy]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 39 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed osteosarcoma at primary diagnosis

• Lesions detected in at least 1 lung that are consistent with metastatic disease and approachable with thoracotomy

• No prior recurrence of osteosarcoma

• No other sites of metastases

• Resectable pulmonary nodule(s), defined as nodule(s) that are removable without performing a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)

• Prior thoracotomy allowed in patients with imaging consistent with metastatic involvement in both lungs provided the lung on which the thoracotomy was performed is disease-free

• No pleural effusion or pleural based nodules

PATIENT CHARACTERISTICS:

Age

• 39 and under

Performance status

• Karnofsky 50-100% (patients over 16 years of age)

• Lansky 50-100% (patients 16 years of age and under)

Life expectancy

• At least 8 weeks

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Pulmonary

• No evidence of dyspnea at rest

• No exercise intolerance

• Pulse oximetry at least 94%

• Baseline Forced expiratory volume in 1 second (FEV_1) at least 80% of predicted

• No history of asthma

• No history of reactive airway disease

• No history of bronchospasm

Other

• Willing and able to perform inhalation therapy

• No medical contraindication to surgical excision

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent immunotherapy

• No other concurrent immunomodulating agents

Chemotherapy

• No concurrent anticancer chemotherapy

Endocrine therapy

• No concurrent steroids by any route

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

• No concurrent thoracoscopy or video-assisted thoracic surgery

Other

• No more than 1 prior treatment regimen for osteosarcoma

• No concurrent participation in another COG therapeutic study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama	United States	35294
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
3	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
4	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Southern California Permanente Medical Group	Downey	California	United States	90242-2814
6	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
7	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90801
8	Children's Hospital and Research Center Oakland	Oakland	California	United States	94609
9	University of California Davis Cancer Center	Sacramento	California	United States	95817
10	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
11	Stanford Cancer Center	Stanford	California	United States	94305-5824
12	Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
13	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
14	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
15	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
16	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
17	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
18	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136
19	Miami Children's Hospital	Miami	Florida	United States	33155
20	Baptist-South Miami Regional Cancer Program	Miami	Florida	United States	33176
21	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
22	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
23	All Children's Hospital	St. Petersburg	Florida	United States	33701
24	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
25	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
26	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
27	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
28	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712-6297
29	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
30	Simmons Cooper Cancer Institute	Springfield	Illinois	United States	62794-9677
31	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
32	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
33	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
34	Kosair Children's Hospital	Louisville	Kentucky	United States	40232
35	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
36	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
37	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
38	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
39	Hurley Medical Center	Flint	Michigan	United States	48503
40	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503-2560
41	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
42	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
43	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
44	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216-4505
45	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
46	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
47	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
48	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
49	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
50	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
51	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
52	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
53	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
54	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
55	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
56	Akron Children's Hospital	Akron	Ohio	United States	44308-1062
57	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
58	Nationwide Children's Hospital	Columbus	Ohio	United States	43205-2696
59	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404-1815
60	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
61	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
62	Oregon Health and Science University Cancer Institute	Portland	Oregon	United States	97239-3098
63	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18107
64	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
65	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-9786
66	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
67	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
68	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina	United States	29203
69	Greenville Hospital Cancer Center	Greenville	South Carolina	United States	29605
70	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37901
71	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
72	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
73	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
74	Covenant Children's Hospital	Lubbock	Texas	United States	79410
75	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
76	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
77	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
78	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
79	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99220-2555
80	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
81	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
82	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
83	Midwest Children's Cancer Center at Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
84	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales	Australia	2145
85	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
86	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
87	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
88	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
89	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
90	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
91	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4
92	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
93	San Jorge Children's Hospital	Santurce		Puerto Rico	00912

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Carola A. Arndt, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00066365
• Other Study ID Numbers: AOST0221; CDR0000315540; COG-AOST0221; NCI-2012-02543; U10CA098543
• First Posted: Aug 7, 2003
• Last Update Posted: Mar 30, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Children's Oncology Group: metastatic osteosarcoma; recurrent osteosarcoma; lung metastases
• Additional relevant MeSH terms: Osteosarcoma; Recurrence; Molgramostim; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy	Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy
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

Baseline Characteristics

Arm/Group Title	Group 1 (Unilateral Recurrence) - Sargramostim and Thoractomy	Group 2 (Bilateral Recurrence) - Sargramostim and Thoractomy	Total
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 Participants	31	18	49
Age (Count of 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%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	16	17	16
Sex: Female, Male (Count of Participants)
Female	15 48.4%	5 27.8%	20 40.8%
Male	16 51.6%	13 72.2%	29 59.2%
Ethnicity (NIH/OMB) (Count of 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%	2 11.1%	2 4.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.2%	0 0%	1 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 22.6%	0 0%	7 14.3%
White	22 71%	16 88.9%	38 77.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.2%	2 11.1%	3 6.1%
Region of Enrollment (participants) [Number]
United States	30 96.8%	18 100%	48 98%
Canada	1 3.2%	0 0%	1 2%

Outcome Measures

1. Primary Outcome

Title	Status of FAS Ligand in Pre-chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	0	14
IHC Category 0	7 22.6%
IHC Category 1	5 16.1%
IHC Category 2	1 3.2%
IHC Category 3	1 3.2%

2. Primary Outcome

Title	Presence of FAS in Pre-chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	0	14
IHC Category 0	5 16.1%
IHC Category 1	5 16.1%
IHC Category 2	2 6.5%
IHC Category 3	2 6.5%

3. Primary Outcome

Title	FAS Ligand in Post Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	22	13
IHC Category 0	16 51.6%	7 38.9%
IHC Category 1	4 12.9%	2 11.1%
IHC Category 2	1 3.2%	2 11.1%
IHC Category 3	1 3.2%	2 11.1%

4. Primary Outcome

Title	FAS Status in Post Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	22	13
IHC Category 0	14 45.2%	5 27.8%
IHC Category 1	4 12.9%	4 22.2%
IHC Category 2	1 3.2%	0 0%
IHC Category 3	3 9.7%	4 22.2%

5. Primary Outcome

Title	CD1a Status in Pre Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	0	7
Negative	5 16.1%
Focally Positive	2 6.5%

6. Primary Outcome

Title	CD1a Status in Post Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	20	7
Negative	8 25.8%	5 27.8%
Focally Positive	12 38.7%	2 11.1%

7. Primary Outcome

Title	S100 Status in Pre Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	0	7
Negative	4 12.9%
Focally Positive	3 9.7%

8. Primary Outcome

Title	S100 Status in Post Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	20	10
Negative	17 54.8%	9 50%
Focally Positive	3 9.7%	1 5.6%

9. Primary Outcome

Title	Clusterin Status in Pre Chemotherapy Sample
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

Outcome Measure Data

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
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
Measure Participants	0	7
Negative	5 16.1%
Focally Positive	2 6.5%

10. Primary Outcome

Title	Clusterin Status in Post Chemotherapy Sample
Time Frame	29 days after start of protocol therapy

Outcome Measure Data

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
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
Measure Participants	20	10
Negative	17 54.8%	7 38.9%
Focally Positive	3 9.7%	3 16.7%

11. Primary Outcome

Title	Event Free Survival (EFS)
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

Outcome Measure Data

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
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
Measure Participants	27	16
Median (95% Confidence Interval) [years]	.57	.33

12. Primary Outcome

Title	Feasibility Success
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

Outcome Measure Data

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
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
Measure Participants	27	16
Yes	24 77.4%	16 88.9%
No	3 9.7%	0 0%

Adverse Events

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)
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1 (Unilateral Recurrence)		Group 2 (Bilateral Recurrence)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/27 (14.8%)		0/16 (0%)
Cardiac disorders
Left ventricular systolic dysfunction	1/27 (3.7%)		0/16 (0%)
Injury, poisoning and procedural complications
Postoperative hemorrhage	1/27 (3.7%)		0/16 (0%)
Investigations
Alanine aminotransferase increased	1/27 (3.7%)		0/16 (0%)
Aspartate aminotransferase increased	1/27 (3.7%)		0/16 (0%)
Creatinine increased	1/27 (3.7%)		0/16 (0%)
Forced expiratory volume decreased	1/27 (3.7%)		0/16 (0%)
Metabolism and nutrition disorders
Hypocalcemia	1/27 (3.7%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/27 (3.7%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders - Other	1/27 (3.7%)		0/16 (0%)
Vascular disorders
Hypotension	1/27 (3.7%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Group 1 (Unilateral Recurrence)		Group 2 (Bilateral Recurrence)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/27 (29.6%)		4/16 (25%)
Blood and lymphatic system disorders
Anemia	1/27 (3.7%)		0/16 (0%)
Blood and lymphatic system disorders - Other	1/27 (3.7%)		0/16 (0%)
General disorders
Non-cardiac chest pain	3/27 (11.1%)		0/16 (0%)
Pain	1/27 (3.7%)		0/16 (0%)
Infections and infestations
Infections and infestations - Other	1/27 (3.7%)		0/16 (0%)
Injury, poisoning and procedural complications
Fracture	1/27 (3.7%)		0/16 (0%)
Investigations
Forced expiratory volume decreased	0/27 (0%)		3/16 (18.8%)
Neutrophil count decreased	1/27 (3.7%)		0/16 (0%)
Platelet count decreased	1/27 (3.7%)		0/16 (0%)
Vital capacity abnormal	0/27 (0%)		2/16 (12.5%)
White blood cell decreased	1/27 (3.7%)		0/16 (0%)
Metabolism and nutrition disorders
Hyperglycemia	1/27 (3.7%)		0/16 (0%)
Hypocalcemia	1/27 (3.7%)		0/16 (0%)
Hypoglycemia	1/27 (3.7%)		0/16 (0%)
Hypokalemia	1/27 (3.7%)		0/16 (0%)
Hyponatremia	1/27 (3.7%)		0/16 (0%)
Hypophosphatemia	1/27 (3.7%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	1/27 (3.7%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/27 (3.7%)		0/16 (0%)
Bronchospasm	1/27 (3.7%)		0/16 (0%)
Cough	2/27 (7.4%)		0/16 (0%)
Dyspnea	2/27 (7.4%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders - Other	1/27 (3.7%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/27 (3.7%)		0/16 (0%)
Vascular disorders
Thromboembolic event	0/27 (0%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior Sponsor approval.