PET CT as Predictor of Response in Preoperative Chemotherapy for Soft Tissue Sarcoma

OBJECTIVES:

Primary

- Determine whether measurements of fludeoxyglucose (FDG) positron emission tomography
(PET)/CT imaging can accurately predict disease-free survival of patients with soft
tissue sarcoma who are receiving neoadjuvant chemotherapy.

Secondary

- Correlate histological response to neoadjuvant chemotherapy for soft tissue sarcomas
with FDG-PET/CT imaging findings.

Tertiary

- Determine the changes in FDG-PET/CT imaging over time as each course of chemotherapy is
given.

OUTLINE: Patients receive 1 of 2 standard chemotherapy regimens:

- Preferred regimen: Patients receive pegylated doxorubicin HCl liposome IV on day 1,
ifosfamide IV continuously on days 1-6, and pegfilgrastim subcutaneously (SC) on day 8.
Treatment repeats every 28 days for up to 4 courses in the absence of disease
progression or unacceptable toxicity.

- Alternative regimen: Patients receive doxorubicin hydrochloride IV continuously on days
1-7. Patients also receive ifosfamide and pegfilgrastim as in the preferred regimen.
Treatment repeats every 28 days for up to 4 courses in the absence of disease
progression or unacceptable toxicity.

All patients undergo a fludeoxyglucose positron emission tomography/CT scan at baseline,
after course 1, and after completion of chemotherapy. Patients undergo surgery within 4-6
weeks after completion of chemotherapy.

After completion of study treatment and surgery, patients are followed every 6 months for 5
years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.

Inclusion Criteria:

- Patients must have histologically confirmed, high grade, soft tissue sarcoma including

- malignant fibrous histiocytoma,

- liposarcoma,

- fibrosarcoma,

- leiomyosarcoma,

- synovial carcinoma,

- malignant peripheral nerve sheath tumor (MPNST),

- epithelioid sarcoma, and

- sarcomas-not otherwise specified.

NOTE: Ewings sarcoma, primitive neuroectodermal tumor, extraskeletal, osteosarcoma,
extraskeletal chondrosarcoma, alveolar soft part sarcoma, rhabdomyosarcoma, carcinosarcoma,
Kaposi's sarcoma, angiosarcoma, and mesothelioma patients are ineligible for this study.

- Measurable disease using traditional cross section measurements with the primary
site's largest diameter > 5 centimeters by positron emission tomography/computated
tomography (PET/CT), CT or magnetic resonance imaging (MRI) scan. Patients with either
localized (primary or locally recurrent) or metastatic disease at presentation are
eligible for study if they are to receive neoadjuvant treatment prior to excision of
the primary (stage IIC, III, IVA, IVB.)

- Age ≥ 16 years, Karnofsky ≥ 70%

- Adequate organ function for receiving chemotherapy as determined by the treating
physician.

- Women of childbearing potential and sexually active males are required to use an
effective method of contraception (ie, a hormonal contraceptive, intra-uterine device,
diaphragm with spermicide, condom with spermicide, or abstinence) during the study.

Exclusion Criteria:

- Previous treatment with chemotherapy or radiation therapy

- Females known to be pregnant or breast-feeding are excluded because PET/CT scan in
pregnant women is not FDA approved.

- Serious concomitant systemic disorders (eg, active infection) that, in the opinion of
the investigator, would compromise the safety of the patient or compromise the
patient's ability to complete the study. Patients with PET-CT as an indicator of
disease survival in soft tissue sarcoma untreated or symptomatic CNS metastases or
uncontrolled diabetes will not be eligible.

Patient must give written informed consent indicating the investigational nature of the
study and its potential risks.