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

NCT00066365 | Completed Phase 2 Results DMC

• 5 other identifiers: AOST0221CDR0000315540COG-AOST0221NCI-2012-02543U10CA098543
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 93

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.

Conditions

Metastatic Cancer; Sarcoma

Keywords

metastatic osteosarcoma; recurrent osteosarcoma; lung metastases

Outcome Measures

Primary Outcomes (12)

• Status of FAS Ligand in Pre-chemotherapy Sample

  FAS ligand (FASL) is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. The Cluster of Differentiation 1a (CD1a) status is measured in Immunohistochemistry (IHC) categories.

  29 days after start of protocol therapy

• Presence of FAS in Pre-chemotherapy Sample

  FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.

  29 days after start of protocol therapy

• FAS Ligand in Post Chemotherapy Sample

  FAS ligand or FASL is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. The presence is measured in Immunohistochemistry (IHC) categories.

  29 days after start of protocol therapy

• FAS Status in Post Chemotherapy Sample

  FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.

  29 days after start of protocol therapy

• CD1a Status in Pre Chemotherapy Sample

  CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.

  29 days after start of protocol therapy

• CD1a Status in Post Chemotherapy Sample

  CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.

  29 days after start of protocol therapy

• S100 Status in Pre Chemotherapy Sample

  The S-100 proteins are a family of low-molecular-weight proteins characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand type") conformation.

  29 days after start of protocol therapy

• S100 Status in Post Chemotherapy Sample

  The S-100 proteins are a family of low-molecular-weight proteins characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand type") conformation.

  29 days after start of protocol therapy

• Clusterin Status in Pre Chemotherapy Sample

  The protein encoded by this gene can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders.

  29 days after start of protocol therapy

• Clusterin Status in Post Chemotherapy Sample

  29 days after start of protocol therapy

• Event Free Survival (EFS)

  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.

  Time of enrollment to Event or 5 years from enrollment, whichever occurs first

• Feasibility Success

  Feasibility success defined as received 21 days of protocol therapy, did not experience grade III or grade IV toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 3 and rendered surgically free of disease in the lungs.

  Enrollment through 21 days of protocol therapy

Study Arms (2)

Group 1 (unilateral recurrence) - Sargramostim and thoractomy

EXPERIMENTAL

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.

Biological: sargramostim; Procedure: conventional surgery

Group 2 (bilateral recurrence) - Sargramostim and thoractomy

EXPERIMENTAL

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.

Biological: sargramostim; Procedure: conventional surgery

Interventions

sargramostim BIOLOGICAL

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

Also known as: aerosol sargramostim, inhaled GM-CSF, Granulocyte Macrophage Colony Stimulating Factor, rhu GM-CSF, rGM-CSF, GM-CSF, Prokine®, Leukine®, Interberin®, NSC#613795

Group 1 (unilateral recurrence) - Sargramostim and thoractomy; Group 2 (bilateral recurrence) - Sargramostim and thoractomy

conventional surgery PROCEDURE

thoracotomy

Group 1 (unilateral recurrence) - Sargramostim and thoractomy; Group 2 (bilateral recurrence) - Sargramostim and thoractomy

Eligibility Criteria

• Age: Up to 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (93)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016-7710, United States

Location

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, 85724-5024, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242-2814, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

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

Long Beach, California, 90801, United States

Location

Children's Hospital and Research Center Oakland

Oakland, California, 94609, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5824, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

Baptist-South Miami Regional Cancer Program

Miami, Florida, 33176, United States

Location

Nemours Children's Clinic - Orlando

Orlando, Florida, 32806, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

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

Savannah, Georgia, 31403-3089, United States

Location

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

Boise, Idaho, 83712-6297, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Simmons Cooper Cancer Institute

Springfield, Illinois, 62794-9677, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

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

Kansas City, Kansas, 66160-7357, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503-2560, United States

Location

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

Grosse Pointe Woods, Michigan, 48236, United States

Location

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, 48910, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Cancer Clinic

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131-5636, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

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

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308-1062, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404-1815, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18107, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, 29203, United States

Location

Greenville Hospital Cancer Center

Greenville, South Carolina, 29605, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37901, United States

Location

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

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, 05401, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99220-2555, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

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

Milwaukee, Wisconsin, 53226, United States

Location

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

San Jorge Children's Hospital

Santurce, 00912, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 20576718 RESULT

MeSH Terms

Conditions

Neoplasm Metastasis; Sarcoma; Osteosarcoma

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Carola A. Arndt, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2003
• First Posted: August 7, 2003
• Study Start: July 1, 2004
• Primary Completion: July 1, 2010
• Study Completion: December 1, 2013
• Last Updated: March 30, 2015
• Results First Posted: March 30, 2015

Record last verified: 2015-03

Locations

AU (2); US (83); CA (7); PR (1)