Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00017121
• Other study ID #: NCCTG-N0071
• Secondary ID: NCI-2012-02385CD
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2001
• Last updated: July 1, 2016
• Start date: May 2002
• Est. completion date: November 2012

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• sargramostim

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Eureka Community Hospital	Eureka	Illinois
United States	Hematology-Oncology Associates of Fredericksburg, Incorporated	Fredericksburg	Virginia
United States	Fremont Memorial Hospital	Fremont	Ohio
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Kewanee Hospital	Kewanee	Illinois
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Lima Memorial Hospital	Lima	Ohio
United States	McDonough District Hospital	Macomb	Illinois
United States	Minnesota Oncology Hematology, PA at Maplewood Cancer Center	Maplewood	Minnesota
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital System	Monroe	Michigan
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Firelands Regional Medical Center	Sandusky	Ohio
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Park Nicollet Health Services	St. Louis Park	Minnesota
United States	United Hospital	St. Paul	Minnesota
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Fulton County Health Center	Wauseon	Ohio
United States	Medical Oncology and Hematology Associates - West Des Moines	West Des Moines	Iowa
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		Up to 6 years	No
Secondary	Progression-free survival		Up to 6 years	No
Secondary	Overall survival		Up to 6 years	No
Secondary	Objective response rate		Up to 6 years	No