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

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Metastatic Cancer; Sarcoma

Treatments: Procedure: conventional surgery; Biological: sargramostim

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00066365

NCI-2012-02543 (Other Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

AOST0221

COG-AOST0221 (Other Identifier)

CDR0000315540 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: Under 39 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 2 patient groups

Group 1 (unilateral recurrence) - Sargramostim and thoractomy

Experimental group

Description:

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.

Treatment:

Procedure: conventional surgery

Biological: sargramostim

Group 2 (bilateral recurrence) - Sargramostim and thoractomy

Experimental group

Description:

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.

Treatment:

Procedure: conventional surgery

Biological: sargramostim