Clinical trial NCT00017121: Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung
Official title: Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Skin)
Metastatic Cancer
Keywords: stage IV melanoma
recurrent melanoma
lung metastases
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Progression-free survival
timeFrame: Up to 6 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: Up to 6 years
measure: Overall survival
timeFrame: Up to 6 years
measure: Objective response rate
timeFrame: Up to 6 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center
state: Iowa
city: West Des Moines
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Lambertville
country: United States
facility: Haematology-Oncology Associates of Ohio and Michigan, PC
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital System
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA at Maplewood Cancer Center
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Health Services
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center Cancer Center
state: North Dakota
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Fremont
country: United States
facility: Fremont Memorial Hospital
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Maumee
country: United States
facility: St. Luke's Hospital
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic - Oregon
state: Ohio
city: Sandusky
country: United States
facility: Firelands Regional Medical Center
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Incorporated
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: Fredericksburg
country: United States
facility: Hematology-Oncology Associates of Fredericksburg, Incorporated
state: Virginia
Study officials:
affiliation: Mayo Clinic
name: Svetomir Markovic, MD, PhD
role: STUDY_CHAIR
References:
citation: Markovic SN, Suman VJ, Nevala WK, Geeraerts L, Creagan ET, Erickson LA, Rowland KM Jr, Morton RF, Horvath WL, Pittelkow MR. A dose-escalation study of aerosolized sargramostim in the treatment of metastatic melanoma: an NCCTG Study. Am J Clin Oncol. 2008 Dec;31(6):573-9. doi: 10.1097/COC.0b013e318173a536.
citation: Markovic SN, Suman VJ, Schaefer P, et al.: Aerosolized sargramostim for the treatment of metastatic melanoma to the lungs. [Abstract] J Clin Oncol 25 (Suppl 18): A-8565, 488s, 2007.