Clinical trial NCT00072280
Conditions: Sarcoma
Keywords: childhood fibrosarcoma nonmetastatic childhood soft tissue sarcoma
Sponsor: Children's Oncology Group
Start date: 2004-11-01; Completion date: 2008-03-01
Enrollment: 7 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed 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.

Arms: arm 1: 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.) arm 2: 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.
Interventions: intervention 1: dactinomycin intervention 2: cyclophosphamide intervention 3: etoposide intervention 4: ifosfamide intervention 5: vincristine sulfate intervention 6: Conventional Surgery intervention 7: MESNA (mercaptoethane sulfonate) intervention 8: Filgrastim
Intervention descriptions: intervention 1: 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 2: Given IV over 60 minutes, dose 25 mg/kg on days 1,22,43 and 64. intervention 3: 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 4: 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 5: 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 6: 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 7: Given orally. Oral daily MESNA dose is equal to at least 60% of the daily cyclophosphamide dose. intervention 8: 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

Protocol documents: