Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00017121

Purpose

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	Intervention	Phase
Melanoma (Skin) Metastatic Cancer	Biological: sargramostim	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Granulocyte-macrophage colony-stimulating factor Sargramostim

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Extent of up-regulation of specific anti-melanoma T cell frequencies (part A) [ Designated as safety issue: No ]
Maximum tolerated dose (part B) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity profile [ Designated as safety issue: Yes ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Objective response rate [ Designated as safety issue: No ]
Percent change from pretreatment levels in other immune parameters [ Designated as safety issue: No ]

Estimated Enrollment:	85
Study Start Date:	May 2002
Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

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 for up to 2 years. 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.

Patients are followed at 3 months, every 2 months for 1 year, and then every 4 months for 5 years.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00017121

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Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Illinois
BroMenn Regional Medical Center
Normal, Illinois, United States, 61761
Cancer Treatment Center at Pekin Hospital
Pekin, Illinois, United States, 61554
Carle Cancer Center at Carle Foundation Hospital
Urbana, Illinois, United States, 61801
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615
Community Cancer Center
Normal, Illinois, United States, 61761
Community Hospital of Ottawa
Ottawa, Illinois, United States, 61350
Eureka Community Hospital
Eureka, Illinois, United States, 61530
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61636
Galesburg Cottage Hospital
Galesburg, Illinois, United States, 61401
Graham Hospital
Canton, Illinois, United States, 61520
Hopedale Medical Complex
Hopedale, Illinois, United States, 61747
Illinois Valley Community Hospital
Peru, Illinois, United States, 61354
Joliet Oncology-Hematology Associates, Limited - West
Joliet, Illinois, United States, 60435
Kewanee Hospital
Kewanee, Illinois, United States, 61443
Mason District Hospital
Havana, Illinois, United States, 62644
McDonough District Hospital
Macomb, Illinois, United States, 61455
Memorial Hospital
Carthage, Illinois, United States, 62321
Galesburg Clinic
Galesburg, Illinois, United States, 61401
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa, Illinois, United States, 61350
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, United States, 61615
OSF St. Francis Medical Center
Peoria, Illinois, United States, 61637
Perry Memorial Hospital
Princeton, Illinois, United States, 61356
Proctor Hospital
Peoria, Illinois, United States, 61614
Rush-Copley Cancer Care Center
Aurora, Illinois, United States, 60507
St. Joseph Medical Center
Bloomington, Illinois, United States, 61701
St. Margaret's Hospital
Spring Valley, Illinois, United States, 61362
United States, Indiana
Saint Anthony Memorial Health Centers
Michigan City, Indiana, United States, 46360
United States, Iowa
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309
Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, United States, 52403
John Stoddard Cancer Center
Des Moines, Iowa, United States, 50316-2301
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates - West Des Moines
West Des Moines, Iowa, United States, 50266
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates at Mercy Cancer Center
Des Moines, Iowa, United States, 50314
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Mercy Capitol Hospital
Des Moines, Iowa, United States, 50307
United States, Michigan
Community Cancer Center of Monroe
Monroe, Michigan, United States, 48162
Haematology-Oncology Associates of Ohio and Michigan, PC
Lambertville, Michigan, United States, 48144
Hickman Cancer Center at Bixby Medical Center
Adrian, Michigan, United States, 49221
Mercy Memorial Hospital System
Monroe, Michigan, United States, 48162
United States, Minnesota
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Hubert H. Humphrey Cancer Center at North Memorial Medical Center
Robbinsdale, Minnesota, United States, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
Minnesota Oncology Hematology, PA at Maplewood Cancer Center
Maplewood, Minnesota, United States, 55109
Park Nicollet Health Services
St. Louis Park, Minnesota, United States, 55416
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
United Hospital
St. Paul, Minnesota, United States, 55102
Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
United States, Nebraska
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, United States, 68124
Creighton University Medical Center
Omaha, Nebraska, United States, 68131-2197
Immanuel Medical Center
Omaha, Nebraska, United States, 68122
United States, North Dakota
Bismarck Cancer Center
Bismarck, North Dakota, United States, 58501
Medcenter One Hospital Cancer Care Center
Bismarck, North Dakota, United States, 58501
Mid Dakota Clinic, PC
Bismarck, North Dakota, United States, 58501
St. Alexius Medical Center Cancer Center
Bismarck, North Dakota, United States, 58502
United States, Ohio
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43617
Firelands Regional Medical Center
Sandusky, Ohio, United States, 44870
Flower Hospital Cancer Center
Sylvania, Ohio, United States, 43560
Fremont Memorial Hospital
Fremont, Ohio, United States, 43420
Fulton County Health Center
Wauseon, Ohio, United States, 43567
Lima Memorial Hospital
Lima, Ohio, United States, 45804
Medical University of Ohio Cancer Center
Toledo, Ohio, United States, 43614
Mercy Hospital of Tiffin
Tiffin, Ohio, United States, 44883
St. Vincent Mercy Medical Center
Toledo, Ohio, United States, 43608
Northwest Ohio Oncology Center
Maumee, Ohio, United States, 43537
St. Charles Mercy Hospital
Oregon, Ohio, United States, 43616
St. Luke's Hospital
Maumee, Ohio, United States, 43537
North Coast Cancer Care, Incorporated
Sandusky, Ohio, United States, 44870
Toledo Clinic - Oregon
Oregon, Ohio, United States, 43616
Toledo Clinic, Incorporated - Main Clinic
Toledo, Ohio, United States, 43623
Toledo Hospital
Toledo, Ohio, United States, 43606
Wood County Oncology Center
Bowling Green, Ohio, United States, 43402
United States, Pennsylvania
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, United States, 18711
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-0001
Geisinger Medical Group - Scenery Park
State College, Pennsylvania, United States, 16801
United States, South Dakota
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105
Medical X-Ray Center, PC
Sioux Falls, South Dakota, United States, 57105
Sioux Valley Hospital and University of South Dakota Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Virginia
Hematology-Oncology Associates of Fredericksburg, Incorporated
Fredericksburg, Virginia, United States, 22401

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Svetomir Markovic, MD, PhD	Mayo Clinic
Investigator:	John H. Donohue, MD	Mayo Clinic
Investigator:	Ellison F. Kalda, MD, FACS	Avera Cancer Institute
Investigator:	Lawrence J. Burgart, MD	Mayo Clinic
Investigator:	Axel Grothey, MD	Mayo Clinic
Investigator:	Muhammed Hussain, MD	Saskatchewan Cancer Agency

Study ID Numbers:	CDR0000068654, NCCTG-N0071
Study First Received:	June 6, 2001
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00017121 History of Changes
Health Authority:	United States: Federal Government