A Randomized Study of the Effect of Adjuvant Chemotherapy With Doxorubicin and Ifosfamide With Mesna in the Treatment of High-Grade Adult Extremity Soft Tissue Sarcoma

Official Title: “A Randomized Study of the Effect of Adjuvant Chemotherapy With Doxorubicin and Ifosfamide With Mesna in the Treatment of High-Grade Adult Extremity Soft Tissue Sarcoma”

Randomized study. All patients must be randomized to treatment on Arms I and II within 3 months of definitive surgery on Regimen A.

Regimen A: Surgery followed, as indicated, by Radiotherapy. Amputation; or limb-sparing resection followed by involved-field irradiation using megavoltage equipment with or without electron boost.

Arm I: 2-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation and Urothelial Protection. Doxorubicin, DOX, NSC-123127; Ifosfamide, IFF, NSC-109724; with Granulocyte Colony Stimulating Factor (Amgen), G-CSF,

NSC-614629; and Mesna, NSC-113891.

Arm II: Observation. No adjuvant chemotherapy.

Patients with primary, high-grade soft tissue sarcoma of the extremities will undergo treatment of their primary tumor with either amputation or limb-sparing surgery and radiotherapy, and then be randomized to either observation or adjuvant treatment with doxorubicin and ifosfamide with mesna (with G-CSF) for five cycles beginning post-operatively. Local recurrence, disease-free survival and overall survival will be evaluated in this randomized two-arm trial.

Intervention(s) in this Clinical Trial

• Drug: doxorubicin
• Drug: ifosfamide
• Drug: mesna

DISEASE CHARACTERISTICS:

• Histologically proven AR and ESFT which includes: Classical, atypical and extraosseous
• Ewing's sarcoma, primitive peripheral neuroectodermal tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma.
• Confirmed presence of tumor-specific infusion protein by documented RT-PCR which corresponds to one of the tumor specific peptides available for vaccination.
• Measurable tumor.
• No prior or current CNS metastases.

PRIOR/CONCURRENT THERAPY:

Arm A patients:

• May be enrolled on the protocol for the first phase in the absence of RT PCR documentation of a tumor-specific fusion protein which corresponds to one of the tumor-specific peptides available for vaccination. However, RT PCR documentation at the time of tumor recurrence must occur prior to administration of immunotherapy. At time of initial tumor diagnosis, prior to any cytoreductive therapy.

Arm B patients:

• Tumor recurrence occurring during or after receiving at least first line cytoreductive therapy for ESFT and AR. No more than two post-recurrence salvage regimens unless peripheral CD4+T cell number is greater than 400 cells per millimeter cubed.
• At least 6 weeks since any treatments and recovered from all acute toxic effects from time in which immunotherapy will be started for this study.
• No concurrent estrogen therapy during immunotherapy section of study.

PATIENT CHARACTERISTICS:

• Age: 2-25 (at time of initial diagnosis of alveolar rhabdomyosarcoma).
• Weight: Greater than 15 kg (at time of apheresis).
• Performance status: ECOG 0-2.
• Life expectancy: At least 8 weeks.

Hematopoietic:

• ANC greater than 100,000/mm3.
• Hemoglobin greater than 9.0 g/dL.
• Platelet count greater than 50,000/mm3.

Hepatic:

• Bilirubin less than 2.0 mg/dL (unless related to involvement by tumor).
• Transaminases less than 3 times normal (unless related to involvement by tumor).

Renal:

• Creatinine less than 1.5 mg/dL or creatinine clearance greater than 60 mL/min.

Cardiovascular:

• No major disorder of cardiovascular system.
• Cardiac ejection fraction greater than 40%.

Pulmonary:

• No major disorder of pulmonary system.

Other:

• Not pregnant or nursing.
• HIV negative.
• Hepatitis B or C negative.
• No patients requiring daily oral corticosteroid therapy.
• If allergic to eggs, egg products, or thimerosal, or have a history of Guillain-Barre syndrome, ineligible to receive influenza vaccine.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Cancer Institute (NCI) NIH

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00001300

Study ID Number: 920210

ClinicalTrials.gov Identifier: NCT00001300

Health Authority: United States: Federal Government