Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	NCCTG-N0071 N0071, NCT00017121

Objectives

1. Determine immunomodulatory effects of aerosolized sargramostim (GM-CSF) in patients with metastatic melanoma to the lung (part A).
2. Determine toxicity profile of this therapy, in terms of pulmonary and hematologic toxicity, in these patients.
3. Determine, preliminarily, the therapeutic effects of this therapy, in terms of progression-free survival, overall survival, and objective response rate, in these patients.
4. Determine the maximum tolerated dose of GM-CSF in these patients (part B).

Entry 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

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

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/mm³
• Platelet count at least 75,000/mm³
• 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)
• FEV₁ 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

Expected Enrollment

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

Outcomes

Extent of up-regulation of specific anti-melanoma T cell frequencies (part A)
Maximum tolerated dose (part B)

Toxicity profile
Progression-free survival
Overall survival
Objective response rate
Percent change from pretreatment levels in other immune parameters

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.

Markovic SN, Suman VJ, Nevala WK, et al.: A dose-escalation study of aerosolized sargramostim in the treatment of metastatic melanoma: an NCCTG Study. Am J Clin Oncol 31 (6): 573-9, 2008.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Svetomir Markovic, MD, PhD, Protocol chair		Ph: 507-284-2511
John Donohue, MD, Protocol co-chair		Ph: 507-284-2511 Email: donohue.john@mayo.edu
Ellison Kalda, MD, FACS, Protocol co-chair		Ph: 605-322-3000
Lawrence Burgart, MD, Protocol co-chair		Ph: 507-284-2511
Axel Grothey, MD, Protocol co-chair		Ph: 507-284-2511 Email: grothey.axel@mayo.edu
Muhammed Hussain, MD, Protocol co-chair		Ph: 306-766-2691

Registry Information
Official Title		Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung
Trial Start Date		2002-05-10
Registered in ClinicalTrials.gov		NCT00017121
Date Submitted to PDQ		2001-04-09
Information Last Verified		2007-04-06
NCI Grant/Contract Number		CA31946

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