Inhaled Sargramostim in Treating Patients With Melanoma Metastatic to the Lung

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00017121
First received: June 6, 2001
Last updated: November 29, 2012
Last verified: April 2007
  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 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung

Resource links provided by NLM:


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: November 2012 (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 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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00017121

  Show 87 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
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:
Publications:
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.

ClinicalTrials.gov Identifier: NCT00017121     History of Changes
Other Study ID Numbers: CDR0000068654, NCCTG-N0071
Study First Received: June 6, 2001
Last Updated: November 29, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
recurrent melanoma
lung metastases

Additional relevant MeSH terms:
Melanoma
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplastic Processes
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Pathologic Processes

ClinicalTrials.gov processed this record on October 30, 2014