Clinical trial NCT00148109
Conditions: Sarcoma
Keywords: Unresectable/metastatic high grade soft tissue bony sarcoma
Sponsor: University of Michigan Rogel Cancer Center
Start date: 2005-06-01; Completion date: 2009-12-01
Enrollment: 36 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to explore how this cancer is affected by a new medication, cetuximab. Cetuximab is directed towards a protein called EGFR (epidermal growth factor receptor), that is found in some types of cancer. Studies have shown that this drug can be beneficial in patients with colon cancer and has been approved by the US Food and Drug Administration (FDA) for this purpose. The researchers are conducting a study to see if it is beneficial in patients with sarcoma.

Detailed description:
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 adults.

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.

Arms: arm 1: The EGFR positive group will be conducted in a 2-stage minimax trial design to determine the rate of four-month progression free survival in this patient population treated with cetuximab arm 2: The EGFR negative group will help us explore the possibility of benefit of cetuximab in a patient whose tumor does not express or minimally expresses EGFR. If benefit in progression-free survival or in another surrogate such as tumor response or a molecular event is seen in this group it would provide rationale to study this group further in subsequent trials
Interventions: intervention 1: Cetuximab intervention 2: Cetuximab
Intervention descriptions: intervention 1: The initial dose of cetuximab is 400 mg/m2 intravenously administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. intervention 2: Cetuximab 400 mg/m2 over 120 min IV initial does followed by weekly Cetuximab 250 mg/m2 over 60 min

Protocol documents: