Phase II Trial of Cetuximab in Patients With Metastatic and/or Locally Advanced Soft Tissue and Bony Sarcomas
Sarcomas are mesenchymal malignancies that arise in the connective tissue throughout the
body and afflict approximately 11,000 people in the United States yearly. Sarcomas are
heterogeneous with well over 50 subtypes described. The peak incidence is subtype-specific
with certain sarcomas seen in children and young adults while other subtypes peak in late
middle-age, causing significant morbidity and mortality in young patients and productive
The precise etiology for most sarcomas remains unknown. External radiation therapy is an
established risk factor. Other risk factors include occupational exposures to certain
chemicals, lymphedema, and hereditary conditions such as neurofibromatosis and Li-Fraumeni
syndrome. Many sarcomas are associated with specific somatic genetic alterations. For
example, some specific subtypes are associated with gene translocations causing aberrant
fusion proteins including Ewing sarcoma (EWS-FLI-1), synovial sarcoma (SSX-SYT), alveolar
rhabdomyosarcoma (PAX3-FHKR), and myxoid liposarcomas (TLS-CHOP). These singular molecular
alterations imply that some sarcomas are cytogenetically simple and may be more appropriate
substrates for therapy targeted to a single molecular pathway.
Sarcomas are commonly present as an asymptomatic mass or with local symptoms in an extremity
or the retroperitoneum. Although tumor size, location, and histologic subtype have been
implicated as prognostic factors in sarcomas, histologic grade remains the most important
factor. Tumor grade is based on the degree of cellularity, differentiation, pleomorphism,
necrosis, and the number of mitoses. Approximately 50-60% of patients with high grade soft
tissue sarcoma will eventually have metastatic disease, as compared to 5-10% of patients
with low grade disease.
Sarcomas spread hematogenously with the most common site of spread being the lung, followed
by liver, bone, and brain. About 50% of patients with sarcoma eventually expire due to
locally advanced or metastatic disease with a median survival of 8-12 months.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients With Sarcoma Who Are Tumor Progression Free and Alive at Four Months From Start of Treatment With Single-agent Cetuximab.
Time of cetuximab administration to clinically documented progression of disease or death assessed for four months after starting cetuximab therapy
Rashmi Chugh, M.D.
University of Michigan
United States: Institutional Review Board
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|