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

University of Minnesota (UMN)

Status: Completed

Conditions: Sarcoma

Treatments: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: ifosfamide; Biological: pegfilgrastim; Radiation: fludeoxyglucose F 18; Drug: doxorubicin hydrochloride; Procedure: conventional surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT00346125

UMN-0512M78446 (Other Identifier)

2005LS080

Details and patient eligibility

About

RATIONALE: Diagnostic procedures, such as positron emission tomography (PET) scan and computated tomography (CT) scan, may help doctors predict a patient's response to treatment and may help plan the best treatment. Drugs used in chemotherapy, such as doxorubicin and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This clinical trial is studying how well PET scan combined with CT scan predicts response in patients undergoing chemotherapy and surgery for soft tissue sarcoma.

Full description

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.

Enrollment: 70 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Preferred Standard Regimen

Active Comparator group

Description:

Subjects with soft tissue sarcoma who are receiving pegylated liposomal doxorubicin hydrochloride, Ifosfamide with mesna and pegfilgrastim - Repeat every 28 days for 4 cycles total

Treatment:

Procedure: conventional surgery

Radiation: fludeoxyglucose F 18

Biological: pegfilgrastim

Drug: pegylated liposomal doxorubicin hydrochloride

Drug: ifosfamide

Alternative Treatment Regimen

Active Comparator group

Description:

Subjects with soft tissue sarcoma who are receiving Doxorubicin hydrochloride, Ifosfamide with mesna and pegfilgrastim - Repeat every 28 days for 4 cycles total

Treatment:

Procedure: conventional surgery

Drug: doxorubicin hydrochloride

Radiation: fludeoxyglucose F 18

Biological: pegfilgrastim

Drug: ifosfamide