Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00066365
First received: August 6, 2003
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

RATIONALE: Inhaling aerosolized sargramostim before and after surgery may interfere with the growth of tumor cells and shrink the tumor so that it can be removed during surgery. Sargramostim may then kill any tumor cells remaining after surgery. This may be an effective treatment for osteosarcoma that has spread to the lung.

PURPOSE: This phase II trial is studying how well inhaled sargramostim works in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung.


Condition Intervention Phase
Metastatic Cancer
Sarcoma
Biological: sargramostim
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Aerosolized GM-CSF (NSC# 613795, IND# 11042) in Patients With First Pulmonary Recurrence of Osteosarcoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Presence of FAS in pre-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of FAS ligand in pre-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of FAS in post-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of CD1a by immunohistochemistry in pre-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of CD1a by immunohistochemistry in post-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of S100 by immunohistochemistry in pre-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of S100 by immunohistochemistry in post-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of Clusterin by immunohistochemistry in pre-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Presence of Clusterin by immunohistochemistry in post-chemotherapy sample [ Time Frame: 29 days after start of protocol therapy ] [ Designated as safety issue: No ]
  • Event Free Survival (EFS) [ Time Frame: Time of enrollment to Event or 5 years from enrollment, whichever occurs first ] [ Designated as safety issue: No ]
    EFS defined as the time from enrollment on the study until disease progression, occurrence of a second malignant neoplasm (SMN), death or last contact, whichever comes first. Disease progression, occurrence of a SMN or death will be considered an analytic even. In all other cases, the patient will be considered censored at last contact.

  • Feasibility Success [ Time Frame: Enrollment through 21 days of protocol therapy ] [ Designated as safety issue: Yes ]
    Feasibility success defined as received 21 days of protocol therapy, did not experience grade III or grade IV toxicity according to CTC AE version 3 and rendered surgically free of disease in the lungs.


Enrollment: 49
Study Start Date: July 2004
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (unilateral recurrence)
(See Detailed Description and Interventions for drugs, dosages, delivery method and frequency.)
Biological: sargramostim
given by inhalation
Other Name: aerosol sargramostim
Procedure: conventional surgery
thoracotomy
Experimental: Group 2 (bilateral recurrence)
(See Detailed Description and Interventions for drugs, dosages, delivery method and frequency.)
Biological: sargramostim
given by inhalation
Other Name: aerosol sargramostim
Procedure: conventional surgery
thoracotomy

Detailed Description:

OBJECTIVES:

Primary

  • Assess the histological findings from patients with first pulmonary recurrence of osteosarcoma who undergo resection of pulmonary metastases after treatment with 2 courses of aerosolized sargramostim (GM-CSF).
  • Determine the event-free survival of patients treated with this drug.
  • Determine whether the maximum tolerated dose in the trial of inhaled GM-CSF in adult patients with melanoma is tolerable in pediatric patients.

Secondary

  • Determine the effect of specific thoracic surgical management on outcome in patients treated with this drug.

OUTLINE: This is a multicenter, dose escalation study. Patients are assigned to 1 of 2 groups according to the extent of pulmonary recurrence (unilateral or bilateral).

  • Group I (unilateral recurrence):

    • Initial inhalation therapy: Patients receive inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses.
    • Thoracotomy: Patients undergo thoracotomy on day 22.
    • Post-thoracotomy inhalation therapy: Beginning on day 29, or as soon as possible thereafter, patients resume inhalation therapy as above for up to 12 additional courses.
  • Group II (bilateral recurrence): Patients may be enrolled on study either before or after the first thoracotomy.

    • First thoracotomy: Patients undergo unilateral thoracotomy.
    • Initial inhalation therapy: Patients receive inhaled GM-CSF, as soon as possible after recovery from first thoracotomy, twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses.
    • Contralateral thoracotomy: Patients undergo contralateral thoracotomy on day 22.
    • Post-thoracotomy inhalation therapy: Beginning on day 29, or as soon as possible, patients resume inhalation therapy as above for up to 12 additional courses.

Treatment in both groups continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 1.6-2 years.

  Eligibility

Ages Eligible for Study:   up to 39 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed osteosarcoma at primary diagnosis

    • Lesions detected in at least 1 lung that are consistent with metastatic disease and approachable with thoracotomy
    • No prior recurrence of osteosarcoma
    • No other sites of metastases
  • Resectable pulmonary nodule(s), defined as nodule(s) that are removable without performing a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
  • Prior thoracotomy allowed in patients with imaging consistent with metastatic involvement in both lungs provided the lung on which the thoracotomy was performed is disease-free
  • No pleural effusion or pleural based nodules

PATIENT CHARACTERISTICS:

Age

  • 39 and under

Performance status

  • Karnofsky 50-100% (patients over 16 years of age)
  • Lansky 50-100% (patients 16 years of age and under)

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Pulmonary

  • No evidence of dyspnea at rest
  • No exercise intolerance
  • Pulse oximetry at least 94%
  • Baseline FEV_1 at least 80% of predicted
  • No history of asthma
  • No history of reactive airway disease
  • No history of bronchospasm

Other

  • Willing and able to perform inhalation therapy
  • No medical contraindication to surgical excision
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No other concurrent immunotherapy
  • No other concurrent immunomodulating agents

Chemotherapy

  • No concurrent anticancer chemotherapy

Endocrine therapy

  • No concurrent steroids by any route

Radiotherapy

  • Not specified

Surgery

  • See Disease Characteristics
  • No concurrent thoracoscopy or video-assisted thoracic surgery

Other

  • No more than 1 prior treatment regimen for osteosarcoma
  • No concurrent participation in another COG therapeutic study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00066365

  Hide Study Locations
Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Children's Hospital and Research Center Oakland
Oakland, California, United States, 94609
University of California Davis Cancer Center
Sacramento, California, United States, 95817
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Stanford Cancer Center
Stanford, California, United States, 94305-5824
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Miami Children's Hospital
Miami, Florida, United States, 33155
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
All Children's Hospital
St. Petersburg, Florida, United States, 33701
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
United States, Idaho
Mountain States Tumor Institute at St. Luke's Regional Medical Center
Boise, Idaho, United States, 83712-6297
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
Simmons Cooper Cancer Institute
Springfield, Illinois, United States, 62794-9677
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States, 40536-0093
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Hurley Medical Center
Flint, Michigan, United States, 48503
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States, 48910
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87131-5636
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308-1062
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205-2696
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital and Health Center and Children's Hospital
Portland, Oregon, United States, 97227
Oregon Health and Science University Cancer Institute
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, United States, 18107
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134-1095
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Palmetto Health South Carolina Cancer Center
Columbia, South Carolina, United States, 29203
Greenville Hospital Cancer Center
Greenville, South Carolina, United States, 29605
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37901
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78207
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Vermont
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05401
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
United States, Wisconsin
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Westmead Institute for Cancer Research at Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1V 4G2
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Carola A. S. Arndt, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00066365     History of Changes
Other Study ID Numbers: AOST0221, CDR0000315540, COG-AOST0221, NCI-2012-02543, U10CA098543
Study First Received: August 6, 2003
Last Updated: November 26, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
metastatic osteosarcoma
recurrent osteosarcoma
lung metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Osteosarcoma
Recurrence
Sarcoma
Neoplastic Processes
Pathologic Processes
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Disease Attributes

ClinicalTrials.gov processed this record on April 16, 2014