Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00017121

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

126.1

Duration (Months)

0.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Inhaling sargramostim may interfere with the growth of tumor cells and may be an effective treatment for melanoma that has spread to the lung.

PURPOSE: This phase I trial is studying the side effects and best dose of inhaled sargramostim in treating patients with melanoma that is metastatic to the lung.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin) Metastatic Cancer	Biological: sargramostim	Phase 1

Detailed Description

OBJECTIVES:

Determine immunomodulatory effects of aerosolized sargramostim (GM-CSF) in patients with metastatic melanoma to the lung (part A).
Determine toxicity profile of this therapy, in terms of pulmonary and hematologic toxicity, in these patients.
Determine, preliminarily, the therapeutic effects of this therapy, in terms of progression-free survival, overall survival, and objective response rate, in these patients.
Determine the maximum tolerated dose of GM-CSF in these patients (part B).

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive aerosolized sargramostim (GM-CSF) twice a day on days 1-7 and 15-21. Treatment repeats every 28 days for 2 courses. Patients with no disease progression after completion of course 2 may continue on treatment until disease progression. Patients are grouped to 1 of 2 dose-escalation regimens (part A vs B).

Part A: Cohorts of 5-10 patients receive escalating doses of GM-CSF until the optimal immunostimulatory dose (ISD) is determined. The optimal ISD is defined as the dose at which at least 7 of 10 patients experience immunostimulation. Once the optimal ISD is determined, 10 patients receive aerosolized GM-CSF at a dose halfway between the optimal ISD and the preceding dose. Dose escalation is discontinued if at least 2 of 5 or at least 4 of 10 patients on a particular dose level experience dose-limiting toxicity.
Part B: Cohorts of 3-6 patients receive escalating doses of GM-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study therapy, patients are followed at 3 months, every 2 months for 1 year, and then every 3-4 months for 5 years.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung

Study Start Date :

May 1, 2002

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sargramostim Patients receive aerosolized sargramostim (GM-CSF) twice a day on days 1-7 and 15-21. Treatment repeats every 28 days for 2 courses. Patients with no disease progression after completion of course 2 may continue on treatment until disease progression. Patients are grouped to 1 of 2 dose-escalation regimens (part A vs B). After completion of study therapy, patients are followed at 3 months, every 2 months for 1 year, and then every 3-4 months for 5 years.	Biological: sargramostim

Arm

Intervention/Treatment

Experimental: sargramostim

Biological: sargramostim

Outcome Measures

Primary Outcome Measures

Progression-free survival [Up to 6 years]

Secondary Outcome Measures

Progression-free survival [Up to 6 years]
Overall survival [Up to 6 years]
Objective response rate [Up to 6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic melanoma to the lung for which no known standard therapy exists
At least 1 unidimensionally measurable lesion
HLA-A2 positive (part A patients only)
Previously treated CNS metastases allowed provided there is no evidence of disease progression within the past 3 months

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

At least 12 weeks

Hematopoietic:

Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 75,000/mm^3
Hemoglobin at least 8.0 g/dL

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)
AST no greater than 3 times ULN

Renal:

Creatinine no greater than 2.5 times ULN

Cardiovascular:

No New York Heart Association class III or IV heart disease

Pulmonary:

No pulmonary disease requiring concurrent active therapy (e.g., supplemental oxygen or bronchodilator)
FEV_1 at least 65% of predicted and at least 1.5 L

Immunologic:

No known immunodeficiency state
No known autoimmune disease
No uncontrolled infection

Other:

No active psychotic disorder requiring pharmacotherapy
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

More than 2 weeks since prior biologic therapy
More than 2 weeks since prior immunotherapy
More than 4 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
No other concurrent biologic therapy or immunotherapy
No concurrent G-CSF
No concurrent GM-CSF other than study drug

Chemotherapy:

More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
No concurrent chemotherapy

Endocrine therapy:

More than 2 weeks since prior corticosteroids
No concurrent glucocorticosteroids

Radiotherapy:

More than 2 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery:

Not specified

Other:

More than 7 days since prior parenteral antibiotics
No concurrent parenteral antibiotics
No concurrent immunosuppressive agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
4	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
5	Graham Hospital	Canton	Illinois	United States	61520
6	Memorial Hospital	Carthage	Illinois	United States	62321
7	Eureka Community Hospital	Eureka	Illinois	United States	61530
8	Galesburg Clinic	Galesburg	Illinois	United States	61401
9	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
10	Mason District Hospital	Havana	Illinois	United States	62644
11	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
12	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
13	Kewanee Hospital	Kewanee	Illinois	United States	61443
14	McDonough District Hospital	Macomb	Illinois	United States	61455
15	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
16	Community Cancer Center	Normal	Illinois	United States	61761
17	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
18	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
19	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
20	Proctor Hospital	Peoria	Illinois	United States	61614
21	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
22	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
23	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
24	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
25	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
26	Perry Memorial Hospital	Princeton	Illinois	United States	61356
27	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
28	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
29	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
30	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
31	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
32	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
33	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
34	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
35	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
36	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
37	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
38	John Stoddard Cancer Center	Des Moines	Iowa	United States	50316-2301
39	Medical Oncology and Hematology Associates - West Des Moines	West Des Moines	Iowa	United States	50266
40	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
41	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
42	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
43	Mercy Memorial Hospital System	Monroe	Michigan	United States	48162
44	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
45	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
46	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
47	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
48	Minnesota Oncology Hematology, PA at Maplewood Cancer Center	Maplewood	Minnesota	United States	55109
49	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
50	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota	United States	55422-2900
51	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
52	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
53	Park Nicollet Health Services	St. Louis Park	Minnesota	United States	55416
54	United Hospital	St. Paul	Minnesota	United States	55102
55	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
56	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
57	Immanuel Medical Center	Omaha	Nebraska	United States	68122
58	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
59	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
60	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
61	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
62	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
63	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
64	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
65	Fremont Memorial Hospital	Fremont	Ohio	United States	43420
66	Lima Memorial Hospital	Lima	Ohio	United States	45804
67	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537
68	St. Luke's Hospital	Maumee	Ohio	United States	43537
69	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
70	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
71	Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
72	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
73	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
74	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
75	Toledo Hospital	Toledo	Ohio	United States	43606
76	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
77	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
78	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
79	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
80	Fulton County Health Center	Wauseon	Ohio	United States	43567
81	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-0001
82	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
83	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
84	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
85	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
86	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota	United States	57117-5039
87	Hematology-Oncology Associates of Fredericksburg, Incorporated	Fredericksburg	Virginia	United States	22401