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

Phase 2

Completed

• Conditions: Sarcoma; Metastatic Cancer

• Registration Number: NCT00066365
• Lead Sponsor: Children's Oncology Group

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.

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.

Study Timeline

• Study First Submitted: 2003-08-06
• Study First Submitted QC: 2003-08-06
• Study First Posted: 2003-08-07
• Study Start: 2004-07
• Primary Completion: 2010-07
• Study Completion: 2013-12
• Results First Submitted: 2015-02-11
• Status Verified: 2015-03
• Results First Submitted QC: 2015-03-17
• Last Update Submitted: 2015-03-17
• Results First Posted: 2015-03-30
• Last Update Posted: 2015-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Clusterin Status in Post Chemotherapy Sample	29 days after start of protocol therapy
Status of FAS Ligand in Pre-chemotherapy Sample	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	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	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	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	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	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	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	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	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.
Event Free Survival (EFS)	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	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.

Trial Locations

Locations (93)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham; 🇺🇸 Birmingham, Alabama, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Arizona Cancer Center at University of Arizona Health Sciences Center; 🇺🇸 Tucson, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Southern California Permanente Medical Group; 🇺🇸 Downey, California, United States

Loma Linda University Cancer Institute at Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital; 🇺🇸 Long Beach, California, United States

Children's Hospital and Research Center Oakland; 🇺🇸 Oakland, California, United States

University of California Davis Cancer Center; 🇺🇸 Sacramento, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Scroll for more (83 remaining)