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

Phase 1
18 Years
Not Enrolling
Melanoma (Skin), Metastatic Cancer

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Trial Information

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


- 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

- 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

- 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.

Inclusion Criteria


- 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



- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- At least 12 weeks


- Absolute neutrophil count at least 1,000/mm^3

- Platelet count at least 75,000/mm^3

- Hemoglobin at least 8.0 g/dL


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

- AST no greater than 3 times ULN


- Creatinine no greater than 2.5 times ULN


- No New York Heart Association class III or IV heart disease


- 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


- No known immunodeficiency state

- No known autoimmune disease

- No uncontrolled infection


- No active psychotic disorder requiring pharmacotherapy

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


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


- 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


- More than 2 weeks since prior radiotherapy

- No concurrent radiotherapy


- Not specified


- More than 7 days since prior parenteral antibiotics

- No concurrent parenteral antibiotics

- No concurrent immunosuppressive agents

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Extent of up-regulation of specific anti-melanoma T cell frequencies (part A)

Safety Issue:


Principal Investigator

Svetomir Markovic, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

May 2002

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • Metastatic Cancer
  • stage IV melanoma
  • recurrent melanoma
  • lung metastases
  • Melanoma
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary



Mayo Clinic Scottsdale Scottsdale, Arizona  85259
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Rush-Copley Cancer Care Center Aurora, Illinois  60507
Joliet Oncology-Hematology Associates, Limited - West Joliet, Illinois  60435
Carle Cancer Center at Carle Foundation Hospital Urbana, Illinois  61801
Saint Anthony Memorial Health Centers Michigan City, Indiana  46360
Cedar Rapids Oncology Associates Cedar Rapids, Iowa  52403
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Minnesota Oncology Hematology, PA - Woodbury Woodbury, Minnesota  55125
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Geisinger Medical Group - Scenery Park State College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre, Pennsylvania  18711
Medical X-Ray Center, PC Sioux Falls, South Dakota  57105
Avera Cancer Institute Sioux Falls, South Dakota  57105
Methodist Medical Center of Illinois Peoria, Illinois  61636
John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines, Iowa  50309
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St. Vincent Mercy Medical Center Toledo, Ohio  43608
Sioux Valley Hospital and University of South Dakota Medical Center Sioux Falls, South Dakota  57117-5134
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
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St. Joseph Medical Center Bloomington, Illinois  61701
Graham Hospital Canton, Illinois  61520
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Community Cancer Center Normal, Illinois  61761
Community Hospital of Ottawa Ottawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa Ottawa, Illinois  61350
Cancer Treatment Center at Pekin Hospital Pekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria, Illinois  61615
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Medical Oncology and Hematology Associates at John Stoddard Cancer Center Des Moines, Iowa  50309
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Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines, Iowa  50314
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Hickman Cancer Center at Bixby Medical Center Adrian, Michigan  49221
Community Cancer Center of Monroe Monroe, Michigan  48162
Mercy Memorial Hospital System Monroe, Michigan  48162
Virginia Piper Cancer Institute at Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
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Park Nicollet Health Services St. Louis Park, Minnesota  55416
Immanuel Medical Center Omaha, Nebraska  68122
Creighton University Medical Center Omaha, Nebraska  68131-2197
Bismarck Cancer Center Bismarck, North Dakota  58501
Wood County Oncology Center Bowling Green, Ohio  43402
Fremont Memorial Hospital Fremont, Ohio  43420
Lima Memorial Hospital Lima, Ohio  45804
St. Luke's Hospital Maumee, Ohio  43537
Northwest Ohio Oncology Center Maumee, Ohio  43537
Toledo Clinic - Oregon Oregon, Ohio  43616
St. Charles Mercy Hospital Oregon, Ohio  43616
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
Firelands Regional Medical Center Sandusky, Ohio  44870
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
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Haematology-Oncology Associates of Ohio and Michigan, PC Lambertville, Michigan  48144
Alegant Health Cancer Center at Bergan Mercy Medical Center Omaha, Nebraska  68124
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Mid Dakota Clinic, PC Bismarck, North Dakota  58501
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Medcenter One Hospital Cancer Care Center Bismarck, North Dakota  58501
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Hematology-Oncology Associates of Fredericksburg, Incorporated Fredericksburg, Virginia  22401