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NCT Number: NCT00066365

Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) 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.

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Key information

Conditions

Metastatic Cancer Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplastic Processes Osteosarcoma Pathologic Processes Pathological Conditions, Signs and Symptoms Sarcoma

Age range

Up to 39 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Westmead Institute for Cancer Research at Westmead Hospital, Westmead, New South Wales, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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

conventional surgery

Procedure

thoracotomy

Primary outcomes

  1. Status of FAS Ligand in Pre-chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

    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.

  2. Presence of FAS in Pre-chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

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

  3. FAS Ligand in Post Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

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

  4. FAS Status in Post Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

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

  5. CD1a Status in Pre Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

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

  6. CD1a Status in Post Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

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

  7. S100 Status in Pre Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

    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.

  8. S100 Status in Post Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

    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.

  9. Clusterin Status in Pre Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

    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.

  10. Clusterin Status in Post Chemotherapy Sample

    Time frame: 29 days after start of protocol therapy

  11. Event Free Survival (EFS)

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

    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.

  12. Feasibility Success

    Time frame: Enrollment through 21 days of protocol therapy

    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.

Sponsors and collaborators

Lead sponsor

Children's Oncology Group

Network

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

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

Important dates

Study start
2004
Primary completion
2010
Study completion
2013
First posted
Aug 7, 2003
Registry last updated
Mar 30, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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