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

Show 87 Study Locations

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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma
lung metastases

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue
Neoplasm Metastasis
Nevi and Melanomas
Neuroendocrine Tumors
Melanoma

ClinicalTrials.gov processed this record on November 27, 2009