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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: July 25, 2014
Last verified: July 2014
  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 ligand 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 Names:
  • aerosol sargramostim
  • inhaled GM-CSF
  • Granulocyte Macrophage Colony Stimulating Factor
  • rhu GM-CSF
  • rGM-CSF
  • GM-CSF
  • Prokine®
  • Leukine®
  • Interberin®
  • NSC#613795
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 Names:
  • aerosol sargramostim
  • inhaled GM-CSF
  • Granulocyte Macrophage Colony Stimulating Factor
  • rhu GM-CSF
  • rGM-CSF
  • GM-CSF
  • Prokine®
  • Leukine®
  • Interberin®
  • NSC#613795
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066365

  Show 93 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Carola A. 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: July 25, 2014
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
Osteosarcoma
Recurrence
Disease Attributes
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplastic Processes
Pathologic Processes
Sarcoma

ClinicalTrials.gov processed this record on November 20, 2014