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

December 13, 2022 updated by: Masonic Cancer Center, University of Minnesota

An Evaluation of PET/CT Imaging as a Predictor of Disease Free Survival Following Neo-Adjuvant Chemotherapy for Soft Tissue Sarcoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Preferred Standard Regimen
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
Biological: pegfilgrastim
will be given at 6 mg subcutaneously (SC) at the end of the mesna infusion
Other Names:
  • Neulasta(R)
Drug: ifosfamide
9 g/m^2 by continuous intravenous (IV) infusion over 6 days beginning on day 1 with mesna 10.5 g/m^2 by continuous IV infusion over 7 days beginning on day 1
Other Names:
  • Ifex
  • Mitoxana
Drug: pegylated liposomal doxorubicin hydrochloride
45 mg/m2 intravenous (IV) Day 1, repeat every 28 days.
Other Names:
  • doxorubicin-hydrochloride-liposome
Procedure: conventional surgery
The surgical procedure will be decided by the treating physician and independent of study participation
Radiation: fludeoxyglucose F 18
FDG is a radioactive sugar equal to a uniform whole-body exposure of approximately 1.5 rem for each scan. Post-operative radiation therapy may be given according to institutional guidelines in patients felt to have close surgical margins.
Other Names:
  • FDG
Active Comparator: Alternative Treatment Regimen
Subjects with soft tissue sarcoma who are receiving Doxorubicin hydrochloride, Ifosfamide with mesna and pegfilgrastim - Repeat every 28 days for 4 cycles total
Biological: pegfilgrastim
will be given at 6 mg subcutaneously (SC) at the end of the mesna infusion
Other Names:
  • Neulasta(R)
Drug: ifosfamide
9 g/m^2 by continuous intravenous (IV) infusion over 6 days beginning on day 1 with mesna 10.5 g/m^2 by continuous IV infusion over 7 days beginning on day 1
Other Names:
  • Ifex
  • Mitoxana
Procedure: conventional surgery
The surgical procedure will be decided by the treating physician and independent of study participation
Radiation: fludeoxyglucose F 18
FDG is a radioactive sugar equal to a uniform whole-body exposure of approximately 1.5 rem for each scan. Post-operative radiation therapy may be given according to institutional guidelines in patients felt to have close surgical margins.
Other Names:
  • FDG
Drug: doxorubicin hydrochloride
65 mg/m^2 by continuous intravenous (IV) infusion over 7 days beginning on day 1
Other Names:
  • Adriamycin
  • Doxorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: Baseline through Survival Event
Compare changes in baseline and follow-up fludeoxyglucose (FDG) positron emission tomography (PET)/CT imaging with disease-free survival by peak SUV and max SUV calculations. Changes in baseline and follow-up PET/CT, based on max SUV calculations, will be compared with disease free survival. Disease free survival will be measured in months from the time of study enrollment until the time that disease recurrence/relapse/progression is recorded.
Baseline through Survival Event

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlate histologic response with FDG-PET/CT imaging
Time Frame: At end of each cycle

The overall histologic response will be defined as:

% histologic response = 100 - % viable tumor in the central slice as assessed histologically It should be noted that the % histologic response is different from % tumor necrosis as it includes an assessment of the % tumor necrosis along with the degenerative changes
At end of each cycle
Compare changes in FDG-PET/CT imaging with disease-free survival by max SUV calculations
Time Frame: Baseline Compared to 1 Cycle and Baseline to After Chemotherapy
Changes in PET/CT from baseline will be compared to PET/CT done after one cycle and after completion of chemotherapy treatment before surgical excision using max SUV calculations.
Baseline Compared to 1 Cycle and Baseline to After Chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Edward Cheng, MD, Masonic Cancer Center, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2006

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2022

Study Registration Dates

First Submitted

June 28, 2006

First Submitted That Met QC Criteria

June 28, 2006

First Posted (Estimate)

June 29, 2006

Study Record Updates

Last Update Posted (Estimate)

December 15, 2022

Last Update Submitted That Met QC Criteria

December 13, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005LS080
  • UMN-0512M78446 (Other Identifier: IRB, University of Minnesota)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe