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

NCT ID: NCT00072280

Last Updated: 2014-09-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-30

Study Completion Date

2008-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemotherapy plus possible surgery

Comprised of patients with disease lesions that are initially unresectable, or resected but with resulting grossly positive margins. All patients receive vincristine sulfate, dactinomycin, and cyclophosphamide (VAC), and mercaptoethane sulfonate (MESNA). Depending on response, patients may receive ifosfamide and etoposide (IE). Filgrastim may also be given, as needed. In addition to Chemotherapy, patients may receive Conventional Surgery.

(See Interventions section for drug dosage and administration details.)

Group Type EXPERIMENTAL

dactinomycin

Intervention Type BIOLOGICAL

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

cyclophosphamide

Intervention Type DRUG

Given IV over 60 minutes, dose 25 mg/kg on days 1,22,43 and 64.

etoposide

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Conventional Surgery

Intervention Type PROCEDURE

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.

MESNA (mercaptoethane sulfonate)

Intervention Type BIOLOGICAL

Given orally. Oral daily MESNA dose is equal to at least 60% of the daily cyclophosphamide dose.

Filgrastim

Intervention Type BIOLOGICAL

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

Surgery only

Comprised of patients with initially resectable disease lesions. All patients undergo Conventional Surgery. Those with a result of clear or microscopically positive margins remain on study in this arm, for observation with no further intervention.

Group Type EXPERIMENTAL

Conventional Surgery

Intervention Type PROCEDURE

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.

Interventions

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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

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV over 60 minutes, dose 25 mg/kg on days 1,22,43 and 64.

Intervention Type DRUG

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.

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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.

Intervention Type PROCEDURE

MESNA (mercaptoethane sulfonate)

Given orally. Oral daily MESNA dose is equal to at least 60% of the daily cyclophosphamide dose.

Intervention Type BIOLOGICAL

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

Intervention Type BIOLOGICAL

Other Intervention Names

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DACT Actinomycin-D Cosmegen NSC #3053 Cytoxan NSC #26271 ETOP VePesid Etopophos VP-16 NSC #141540 Isophosphamide Iphosphamide Z4942 Ifex NSC #109724 Oncovin VCR LCR NSC #67574 Sodium 2-mercaptoethane sulfonate UCB 3983 Mesnex NSC #113891 Granulocyte Colony-Stimulating Factor r-metHuG-CSF G-CSF Neupogen NSC #614629

Eligibility Criteria

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Inclusion Criteria

* 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
Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mignon Loh, MD

Role: STUDY_CHAIR

University of California, San Francisco

Anne B. Warwick, MD, MPH

Role: STUDY_CHAIR

Medical College of Wisconsin

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Long Beach, California, United States

Site Status

Kaiser Permanente Medical Center - Oakland

Sacramento, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Comprehensive Cancer Center - Stanford

Stanford, California, United States

Site Status

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

Farmington, Connecticut, United States

Site Status

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Spectrum Health Hospital - Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center & Children's Hospital - Fairview

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Overlook Hospital

Morristown, New Jersey, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Columbus Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Medical Center - Dayton

Dayton, Ohio, United States

Site Status

Tod Children's Hospital - Forum Health

Youngstown, Ohio, United States

Site Status

OU Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Greenville Hospital System Cancer Center

Greenville, South Carolina, United States

Site Status

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Baylor University Medical Center - Houston

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Women's and Children's Hospital

North Adelaide, South Australia, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Starship Children's Health

Auckland, , New Zealand

Site Status

Countries

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United States Australia Canada New Zealand

Other Identifiers

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CDR0000339565

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-02561

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ARST03P1

Identifier Type: OTHER

Identifier Source: secondary_id

ARST03P1

Identifier Type: -

Identifier Source: org_study_id

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