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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00066365




Trial ID
NCT00066365
Ethics application status
Date submitted
6/08/2003
Date registered
6/08/2003
Date last updated
17/03/2015

Titles & IDs
Public title
Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma
Scientific title
A Phase II Study of Aerosolized GM-CSF (NSC# 613795, IND# 11042) in Patients With First Pulmonary Recurrence of Osteosarcoma
Secondary ID [1] 0 0
CDR0000315540
Secondary ID [2] 0 0
AOST0221
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Cancer 0 0
Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - sargramostim
Treatment: Surgery - conventional surgery

Experimental: 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.

Experimental: 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.


Other 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.

Treatment: Surgery: conventional surgery
thoracotomy

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
29 days after start of protocol therapy
Primary outcome [2] 0 0
Presence of FAS in Pre-chemotherapy Sample - FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.
Timepoint [2] 0 0
29 days after start of protocol therapy
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
29 days after start of protocol therapy
Primary outcome [4] 0 0
FAS Status in Post Chemotherapy Sample - FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.
Timepoint [4] 0 0
29 days after start of protocol therapy
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
29 days after start of protocol therapy
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
29 days after start of protocol therapy
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
29 days after start of protocol therapy
Primary outcome [8] 0 0
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.
Timepoint [8] 0 0
29 days after start of protocol therapy
Primary outcome [9] 0 0
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.
Timepoint [9] 0 0
29 days after start of protocol therapy
Primary outcome [10] 0 0
Clusterin Status in Post Chemotherapy Sample
Timepoint [10] 0 0
29 days after start of protocol therapy
Primary outcome [11] 0 0
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.
Timepoint [11] 0 0
Time of enrollment to Event or 5 years from enrollment, whichever occurs first
Primary outcome [12] 0 0
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.
Timepoint [12] 0 0
Enrollment through 21 days of protocol therapy

Eligibility
Key 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
Minimum age
No limit
Maximum age
39 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Westmead Institute for Cancer Research at Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Idaho
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Kentucky
Country [14] 0 0
United States of America
State/province [14] 0 0
Maryland
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Minnesota
Country [18] 0 0
United States of America
State/province [18] 0 0
Mississippi
Country [19] 0 0
United States of America
State/province [19] 0 0
Missouri
Country [20] 0 0
United States of America
State/province [20] 0 0
New Jersey
Country [21] 0 0
United States of America
State/province [21] 0 0
New Mexico
Country [22] 0 0
United States of America
State/province [22] 0 0
New York
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Ohio
Country [25] 0 0
United States of America
State/province [25] 0 0
Oklahoma
Country [26] 0 0
United States of America
State/province [26] 0 0
Oregon
Country [27] 0 0
United States of America
State/province [27] 0 0
Pennsylvania
Country [28] 0 0
United States of America
State/province [28] 0 0
South Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
Tennessee
Country [30] 0 0
United States of America
State/province [30] 0 0
Texas
Country [31] 0 0
United States of America
State/province [31] 0 0
Vermont
Country [32] 0 0
United States of America
State/province [32] 0 0
Washington
Country [33] 0 0
United States of America
State/province [33] 0 0
Wisconsin
Country [34] 0 0
Canada
State/province [34] 0 0
Manitoba
Country [35] 0 0
Canada
State/province [35] 0 0
Nova Scotia
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
Canada
State/province [38] 0 0
Saskatchewan
Country [39] 0 0
Puerto Rico
State/province [39] 0 0
Santurce

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00066365
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carola A. Arndt, MD
Address 0 0
Mayo Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries