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

NCT ID: NCT00066365

Last Updated: 2015-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2013-12-31

Brief Summary

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.

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.

Conditions

Metastatic Cancer; Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1 (unilateral recurrence) - Sargramostim and thoractomy

Patients receive initial inhalation therapy inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every other week every 14 days for a total of 2 courses. Patients undergo surgical procedure thoracotomy on day 22. Beginning on day 29, or as soon as possible thereafter, patients begin post-thoracotomy inhalation therapy for up to 12 additional courses. Treatment 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.

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery

Intervention Type: PROCEDURE

thoracotomy

Group 2 (bilateral recurrence) - Sargramostim and thoractomy

Patients may be enrolled on study either before or after the first thoracotomy procedure. For the first thoracotomy, patients undergo surgical procedure unilateral thoracotomy. Patients receive initial inhalation therapy 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. Patients undergo surgical procedure contralateral thoracotomy on day 22. Beginning on day 29, or as soon as possible, patients begin post-thoracotomy inhalation therapy as above for up to 12 additional courses. Treatment 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.

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

conventional surgery

Intervention Type: PROCEDURE

thoracotomy

Interventions

sargramostim

given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

Intervention Type: BIOLOGICAL

conventional surgery

thoracotomy

Intervention Type: PROCEDURE

Other Intervention Names

aerosol sargramostim; inhaled GM-CSF; Granulocyte Macrophage Colony Stimulating Factor; rhu GM-CSF; rGM-CSF; GM-CSF; Prokine®; Leukine®; Interberin®; NSC#613795

Eligibility Criteria

Inclusion 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 Forced expiratory volume in 1 second (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

• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carola A. Arndt, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Southern California Permanente Medical Group

Downey, California, United States

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Long Beach, California, United States

Children's Hospital and Research Center Oakland

Oakland, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Stanford Cancer Center

Stanford, California, United States

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Nemours Children's Clinic

Jacksonville, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Miami Children's Hospital

Miami, Florida, United States

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

All Children's Hospital

St. Petersburg, Florida, United States

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Simmons Cooper Cancer Institute

Springfield, Illinois, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Kosair Children's Hospital

Louisville, Kentucky, United States

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Akron Children's Hospital

Akron, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Medical Center - Dayton

Dayton, Ohio, United States

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, United States

Oregon Health and Science University Cancer Institute

Portland, Oregon, United States

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, United States

Greenville Hospital Cancer Center

Greenville, South Carolina, United States

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Covenant Children's Hospital

Lubbock, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

CCOP - Scott and White Hospital

Temple, Texas, United States

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

CancerCare Manitoba

Winnipeg, Manitoba, Canada

IWK Health Centre

Halifax, Nova Scotia, Canada

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Hopital Sainte Justine

Montreal, Quebec, Canada

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

San Jorge Children's Hospital

Santurce, , Puerto Rico

Countries

United States; Australia; Canada; Puerto Rico

References

Arndt CA, Koshkina NV, Inwards CY, Hawkins DS, Krailo MD, Villaluna D, Anderson PM, Goorin AM, Blakely ML, Bernstein M, Bell SA, Ray K, Grendahl DC, Marina N, Kleinerman ES. Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma: effects on disease-free survival and immunomodulation. a report from the Children's Oncology Group. Clin Cancer Res. 2010 Aug 1;16(15):4024-30. doi: 10.1158/1078-0432.CCR-10-0662. Epub 2010 Jun 24.

Reference Type: RESULT

PMID: 20576718 (View on PubMed)

Other Identifiers

CDR0000315540

Identifier Type: OTHER

Identifier Source: secondary_id

COG-AOST0221

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-02543

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AOST0221

Identifier Type: -

Identifier Source: org_study_id