Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Fibrosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Vincristine

Ifosfamide

Lenograstim

Dactinomycin

Etoposide phosphate

Isophosphamide mustard

Mesna

Mechlorethamine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Adjuvants, Immunologic

Tubulin Modulators

Antimitotic Agents

Protective Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

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.)

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.

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

dactinomycin

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

cyclophosphamide

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.

etoposide

Given IV over 1 hour, dose 60mg/kg in D5 1/4 NS 10 cc/kg IV on days 1-5 of IE Cycle

ifosfamide

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

vincristine sulfate

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.

Conventional Surgery

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

MESNA (mercaptoethane sulfonate)

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

Filgrastim

Mignon Loh, MD

Anne B. Warwick, MD, MPH

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.

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.

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

A Pilot Phase II Study for Children With Infantile Fibrosarcoma

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).

National Cancer Institute (NCI)

Children's Oncology Group

All eligible patients were considered in the evaluation of adverse events (AEs). Three (3) patients were considered ineligible. All other patients (two on each study arm) are included in AE reporting.

Chemotherapy Plus Possible Surgery

Surgery Only

Total

Age, Categorical

Less than 6 months

6 months or more

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

Australia

Region of Enrollment

Study closed early due to slow accrual. Analysis plans were not carried out (lack of statistical precision compromised the ability to draw appropriate conclusions). Reported Primary Outcome Measure data reflects data collection through March 2008.

Results Reporting Coordinator

Failed

Failure-free through 5 years of follow-up

Failure-free at cutoff (if < 5 years follow-up)

Withdrew from study

Lost to follow-up

By protocol design, only eligible patients were considered in the evaluation for the primary outcome measure. One (1) patient was found ineligible, leaving two (2) for the analysis population.

Failure-free Survival (FFS) in "Chemotherapy Plus Possible Surgery" Arm

Treatment

Follow-up

Spots Global Cancer Trial Database for mesna (mercaptoethane sulfonate)