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Metastatic CancerPhase 2NCT00066365

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

A Phase 2 study testing sargramostim and conventional surgery in people with Metastatic Cancer and Sarcoma, run by Children's Oncology Group at 93 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 39 years
Conditions the study is for
Metastatic Cancer, Sarcoma
What is being tested?
sargramostim and conventional surgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
93 sitesin 4 countries
Study dates
Jul 2004to Dec 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 39 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

93 sites in 4 countries.

93 sites in 4 countries

United States83 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308-1062

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87131-5636

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

    Baltimore, Maryland, 21215

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18107

  • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

    Birmingham, Alabama, 35294

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

    Boise, Idaho, 83712-6297

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

    Boston, Massachusetts, 02115

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Fletcher Allen Health Care - University Health Center Campus

    Burlington, Vermont, 05401

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Palmetto Health South Carolina Cancer Center

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

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

    Dallas, Texas, 75390

  • Children's Medical Center - Dayton

    Dayton, Ohio, 45404-1815

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Southern California Permanente Medical Group

    Downey, California, 90242-2814

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Lee Cancer Care of Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Butterworth Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503-2560

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Greenville Hospital Cancer Center

    Greenville, South Carolina, 29605

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

    Grosse Pointe Woods, Michigan, 48236

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • M. D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

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

    Kansas City, Kansas, 66160-7357

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Children's Hospital

    Knoxville, Tennessee, 37901

  • Breslin Cancer Center at Ingham Regional Medical Center

    Lansing, Michigan, 48910

  • Lucille P. Markey Cancer Center at University of Kentucky

    Lexington, Kentucky, 40536-0093

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Loma Linda, California, 92354

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

    Long Beach, California, 90801

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

    Madison, Wisconsin, 53792-6164

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Baptist-South Miami Regional Cancer Program

    Miami, Florida, 33176

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

    Milwaukee, Wisconsin, 53226

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

    New Brunswick, New Jersey, 08903

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Children's Hospital and Research Center Oakland

    Oakland, California, 94609

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Sacred Heart Cancer Center at Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-9786

  • St. Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134-1095

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016-7710

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Legacy Emanuel Hospital and Health Center and Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University Cancer Institute

    Portland, Oregon, 97239-3098

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

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

    Rochester, New York, 14642

  • University of California Davis Cancer Center

    Sacramento, California, 95817

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78207

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

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

    Savannah, Georgia, 31403-3089

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Providence Cancer Center at Sacred Heart Medical Center

    Spokane, Washington, 99220-2555

  • Simmons Cooper Cancer Institute

    Springfield, Illinois, 62794-9677

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stanford Cancer Center

    Stanford, California, 94305-5824

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

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

    Tampa, Florida, 33607

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Arizona Cancer Center at University of Arizona Health Sciences Center

    Tucson, Arizona, 85724-5024

  • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

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

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada7 sites

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Montreal Children's Hospital at McGill University Health Center

    Montreal, Quebec, H3H 1P3

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1V 4G2

  • Saskatoon Cancer Centre at the University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 4H4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia2 sites

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

  • Westmead Institute for Cancer Research at Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

Puerto Rico1 site

  • San Jorge Children's Hospital

    Santurce, 00912

Other trials in Puerto Rico

About this study

Official title: A Phase II Study of Aerosolized GM-CSF (NSC# 613795, IND# 11042) in Patients With First Pulmonary Recurrence of Osteosarcoma

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.

Read the 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.

Keywords
metastatic osteosarcoma, recurrent osteosarcoma, lung metastases
Medical subject headings
Neoplasm Metastasis, Sarcoma, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sargramostimBiological

    Also called aerosol sargramostim, inhaled GM-CSF, Granulocyte Macrophage Colony Stimulating Factor, rhu GM-CSF

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

  • conventional surgeryProcedure or surgery

    thoracotomy

Study groups in NCT00066365
Study groupRoleWhat they receive
Group 1 (unilateral recurrence) - Sargramostim and thoractomyExperimentalPatients 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.
Receives: Biological: sargramostim; Procedure: conventional surgery
Group 2 (bilateral recurrence) - Sargramostim and thoractomyExperimentalPatients 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.
Receives: Biological: sargramostim; Procedure: conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 29 days after start of protocol therapy

  2. Presence of FAS in Pre-chemotherapy Sample

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

    Measured: 29 days after start of protocol therapy

  3. 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.

    Measured: 29 days after start of protocol therapy

  4. FAS Status in Post Chemotherapy Sample

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

    Measured: 29 days after start of protocol therapy

  5. 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.

    Measured: 29 days after start of protocol therapy

  6. 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.

    Measured: 29 days after start of protocol therapy

  7. 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.

    Measured: 29 days after start of protocol therapy

  8. 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.

    Measured: 29 days after start of protocol therapy

  9. 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.

    Measured: 29 days after start of protocol therapy

  10. Clusterin Status in Post Chemotherapy Sample

    Measured: 29 days after start of protocol therapy

  11. 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.

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

  12. 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.

    Measured: Enrollment through 21 days of protocol therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2003 (estimated)
  2. Study startJul 2004
  3. Primary completionJul 2010
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00066365
Sponsor's protocol ID
AOST0221
Other IDs
CDR0000315540, COG-AOST0221, NCI-2012-02543, U10CA098543
Status last verified
Mar 2015
First submitted
6 Aug 2003
Last updated
30 Mar 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20576718

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sargramostim and conventional surgery in people with Metastatic Cancer and Sarcoma, run by Children's Oncology Group at 93 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 93 sites in United States, Canada, Australia, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Status of FAS Ligand in Pre-chemotherapy Sample (time frame: 29 days after start of protocol therapy). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00066365, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2015.

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