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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066365
• Other study ID #: AOST0221
• Secondary ID: CDR0000315540COG
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2003
• Last updated: March 17, 2015
• Start date: July 2004
• Est. completion date: December 2013

Study information

• Verified date: March 2015
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2013
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 39 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Osteosarcoma
• Sarcoma

Intervention

Biological:
• sargramostim
given by inhalation, dosage escalation Level 1 Dose: 240 micrograms, Level 2 Dose: 1,000 micrograms, and Level 3 Dose: 1,750 micrograms.

Procedure:
• conventional surgery
thoracotomy

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Puerto Rico	San Jorge Children's Hospital	Santurce
United States	Akron Children's Hospital	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Greenville Hospital Cancer Center	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
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	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Midwest Children's Cancer Center at Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital and Research Center Oakland	Oakland	California
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of California Davis Cancer Center	Sacramento	California
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Simmons Cooper Cancer Institute	Springfield	Illinois
United States	All Children's Hospital	St. Petersburg	Florida
United States	Stanford Cancer Center	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico, 

References & Publications (1)

Arndt CA, Koshkina NV, Inwards CY, Hawkins DS, Krailo MD, Villaluna D, Anderson PM, Goorin AM, Blakely ML, Bernstein M, Bell SA, Ray K, Grendahl DC, Marina N, Kleinerman ES. Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Status of FAS Ligand in Pre-chemotherapy Sample	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.	29 days after start of protocol therapy	No
Primary	Presence of FAS in Pre-chemotherapy Sample	FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.	29 days after start of protocol therapy	No
Primary	FAS Ligand in Post Chemotherapy Sample	FAS ligand or FASL is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. The presence is measured in Immunohistochemistry (IHC) categories.	29 days after start of protocol therapy	No
Primary	FAS Status in Post Chemotherapy Sample	FAS/APO-1 is a transmembrane receptor. The presence is measured in Immunohistochemistry (IHC) categories.	29 days after start of protocol therapy	No
Primary	CD1a Status in Pre Chemotherapy Sample	CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.	29 days after start of protocol therapy	No
Primary	CD1a Status in Post Chemotherapy Sample	CD1a (Cluster of Differentiation 1a) is a human protein encoded by the CD1A gene, presence is measured by positivity.	29 days after start of protocol therapy	No
Primary	S100 Status in Pre Chemotherapy Sample	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.	29 days after start of protocol therapy	No
Primary	S100 Status in Post Chemotherapy Sample	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.	29 days after start of protocol therapy	No
Primary	Clusterin Status in Pre Chemotherapy Sample	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.	29 days after start of protocol therapy	No
Primary	Clusterin Status in Post Chemotherapy Sample		29 days after start of protocol therapy	No
Primary	Event Free Survival (EFS)	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.	Time of enrollment to Event or 5 years from enrollment, whichever occurs first	No
Primary	Feasibility Success	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.	Enrollment through 21 days of protocol therapy	Yes