A Phase II Study of Aerosolized GM-CSF (NSC# 613795, IND# 11042) in Patients With First Pulmonary Recurrence of Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 93
- 主要终点
- Status of FAS Ligand in Pre-chemotherapy Sample
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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
- •Not specified
- •Not specified
- •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
- •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
- •See Disease Characteristics
- •No concurrent thoracoscopy or video-assisted thoracic surgery
- •No more than 1 prior treatment regimen for osteosarcoma
- •No concurrent participation in another COG therapeutic study
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: conventional surgery (Procedure)
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.
干预措施: conventional surgery (Procedure)
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.
干预措施: sargramostim (Biological)
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.
干预措施: sargramostim (Biological)
结局指标
主要结局
Status of FAS Ligand in Pre-chemotherapy Sample
时间窗: 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.
Presence of FAS in Pre-chemotherapy Sample
时间窗: 29 days after start of protocol therapy
FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.
FAS Ligand in Post Chemotherapy Sample
时间窗: 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.
FAS Status in Post Chemotherapy Sample
时间窗: 29 days after start of protocol therapy
FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.
CD1a Status in Pre Chemotherapy Sample
时间窗: 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.
CD1a Status in Post Chemotherapy Sample
时间窗: 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.
S100 Status in Pre Chemotherapy Sample
时间窗: 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.
S100 Status in Post Chemotherapy Sample
时间窗: 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.
Clusterin Status in Pre Chemotherapy Sample
时间窗: 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.
Clusterin Status in Post Chemotherapy Sample
时间窗: 29 days after start of protocol therapy
Event Free Survival (EFS)
时间窗: 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.
Feasibility Success
时间窗: 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.
次要结局
未报告次要终点