Surgery and/or Chemotherapy in Treating Children With Infantile, Congenital, or Childhood Fibrosarcoma

Sarcoma Clinical Trial

Official title:

A Pilot Phase II Study for Children With Infantile Fibrosarcoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00072280
• Other study ID #: ARST03P1
• Secondary ID: CDR0000339565NCI
• Status: Terminated
• Phase: Phase 2
• First received: November 4, 2003
• Last updated: September 16, 2014
• Start date: November 2004
• Est. completion date: March 2008

Study information

• Verified date: September 2014
• 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: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well surgery and/or combination chemotherapy work in treating children with fibrosarcoma.

Description:

OBJECTIVES:

Primary

• Determine the event-free and relapse-free survival of children with initially unresectable congenital, infantile, or childhood fibrosarcoma treated with neoadjuvant chemotherapy comprising vincristine, dactinomycin, and cyclophosphamide (VAC) before definitive local control.

Secondary

• Determine the event-free and relapse-free survival of patients initially treated with this regimen followed by observation after local control with positive microscopic margins.

• Determine the event-free and relapse-free survival of patients initially treated with this regimen followed by additional chemotherapy comprising etoposide and ifosfamide after local control with gross positive margins.

• Determine the event-free and relapse-free survival of patients treated with surgery alone.

OUTLINE: This is a pilot, multicenter study. Patients begin treatment according to lesion resectability.

Patients with resectable lesions proceed to surgery.

• Surgery: Patients undergo resection of disease lesions. Patients with clear or microscopically positive margins undergo observation only. Patients with grossly positive margins undergo re-resection if feasible. Patients with grossly positive margins after re-resection or for whom re-resection is not feasible receive chemotherapy comprising vincristine, dactinomycin, and cyclophosphamide (VAC).

Patients with unresectable lesions receive VAC chemotherapy.

• VAC chemotherapy: Patients receive vincristine intravenously (IV) on days 1, 8, and 15 and dactinomycin IV and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with disease progression after 2-4 courses of VAC chemotherapy proceed to chemotherapy comprising etoposide and ifosfamide (IE).

Patients with stable disease after 4 courses of VAC chemotherapy proceed to IE chemotherapy.

Patients with a partial response (PR) and unresectable lesions after 4 courses of VAC chemotherapy receive 2 additional courses of VAC and are then re-evaluated. Patients proceed to surgery if they continue to have a PR or achieve a complete response (CR) and lesions are now resectable.

Patients with a CR or PR and resectable lesions after 4 courses of VAC chemotherapy proceed to surgery.

Patients with stable disease, progressive disease, or a PR and unresectable lesions after 6 courses of VAC proceed to IE chemotherapy.

• IE chemotherapy: Patients receive etoposide IV over 1 hour and ifosfamide IV over 1 hour on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with a CR or PR and resectable lesions after 2-4 courses of IE chemotherapy proceed to surgery.

All patients are followed every 3 months for 6 months, every 6 months for 1 year, and then as clinically indicated.

PROJECTED ACCRUAL: A total of 60-70 patients will be accrued for this study within 8 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 2 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed infantile, congenital, or pediatric fibrosarcoma

• Initial biopsy or surgery performed within the past 35 days

• No evidence of distant metastases

• Available tissue for central review

PATIENT CHARACTERISTICS:

Age

• Under 2 at diagnosis

Performance status

• Zubrod Score (ECOG)

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 100,000/mm^3*

• Hemoglobin at least 10.0 g/dL* NOTE: *Transfusions allowed

Hepatic

• Total bilirubin no greater than 1.5 times upper limit of normal (ULN) (patients over 4 weeks of age)

• Patients under 4 weeks of age with an indirect hyperbilirubinemia are eligible, provided the following criteria are met:

• At least 2 bilirubin values at separate timepoints show a decrease in measurement

• Direct bilirubin is no greater than 20% of the total bilirubin

• Direct bilirubin no greater than 1.5 times ULN

• Alanine Aminotransferase (ALT) less than 2.5 times ULN

Renal

• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

PRIOR/CONCURRENT THERAPY:

Biologic therapy

• No concurrent sargramostim (GM-CSF)

Chemotherapy

• No prior chemotherapy

• No other concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior or concurrent radiotherapy except emergent radiotherapy for impending tracheal compression

Surgery

• See Disease Characteristics

Study Design

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

Related Conditions & MeSH terms

• Fibrosarcoma
• Sarcoma

Intervention

Biological:
• dactinomycin
Given Slow intravenous (IV) push over 1-5 minutes, dose < 1yr 0.025 mg/kg > or = 1 yr 0.045 mg/kg (max dose 2.5 mg) on days 1,22,43 and 64

Drug:
• cyclophosphamide
Given IV over 60 minutes, dose 25 mg/kg on days 1,22,43 and 64.
• etoposide
Given IV over 1 hour, dose 3.3 mg/kg in normal saline (NS) 10 cc/kg (or to equal 0.4 mg/mL concentration) on days 1-5 of IE cycle.
• ifosfamide
Given IV over 1 hour, dose 60mg/kg in D5 1/4 NS 10 cc/kg IV on days 1-5 of IE Cycle
• vincristine sulfate
Given IV Push over 1 minute, dose 0.05 mg/kg (max dose 2 mg) on days 1,8,15,22,29,36,43,50,57 and 64

Procedure:
• Conventional Surgery
Applied only when lesion is resectable. Surgery is the primary means of local control in this study and reasonable attempts at achieving clear margins with an "envelope" of normal tissue should be undertaken at the initial and/or subsequent resections.

Biological:
• MESNA (mercaptoethane sulfonate)
Given orally. Oral daily MESNA dose is equal to at least 60% of the daily cyclophosphamide dose.
• Filgrastim
Given IV - Only use filgrastim if chemotherapy has been delayed or modified for hematologic toxicity, or if patient experiences a significant life-threatening toxicity due to bone marrow suppression

Locations

Country	Name	City	State
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
New Zealand	Starship Children's Health	Auckland
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Southern California Permanente Medical Group	Downey	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Greenville Hospital System 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	Baylor University Medical Center - Houston	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
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	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center & Children's Hospital - Fairview	Minneapolis	Minnesota
United States	Overlook Hospital	Morristown	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	OU Cancer Institute	Oklahoma City	Oklahoma
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	All Children's Hospital	St. Petersburg	Florida
United States	Stanford Comprehensive Cancer Center - Stanford	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	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Tod Children's Hospital - Forum Health	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free Survival (FFS) in "Chemotherapy Plus Possible Surgery" Arm	Failure is defined as the occurrence of one of the following: disease progression, defined as at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions; relapse (defined with same criteria as for disease progression) after response; or death as a first event. Data will be summarized as number of eligible patients in each of the following categories at the time of data cutoff for analyses of 5-year FFS: 1)Failed; 2)Failure-free through 5 years of follow-up; 3)Failure-free until data cutoff (if less than 5 years of follow-up); 4)Withdrew from study; 5)Lost to follow-up. NOTE: Reported data are through March 2008 (see Caveats section).	Study enrollment until failure, completion of follow-up, or completion of 5-year FFS analyses (up to 5 years)	No