Clinical trial NCT00148109: Trial of Cetuximab in Patients With Metastatic and/or Locally Advanced Soft Tissue and Bony Sarcomas
Official title: Phase II Trial of Cetuximab in Patients With Metastatic and/or Locally Advanced Soft Tissue and Bony Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: Unresectable/metastatic high grade soft tissue bony sarcoma
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Eli Lilly and Company
First posted: 2005-09-07
Enrollment: 36
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

To be eligible for the study, patients must fulfill all of the following criteria:

1. Patients must have the ability to give informed consent and have signed an approved informed consent form.
2. Patients must have a pathologic diagnosis of soft tissue sarcoma or bony sarcoma.
3. Patients with tumor tissue available for assessment of EGFR status performed by immunohistochemistry (IHC).
4. Patients with Zubrod performance status 0-2.
5. Patients must be 16 years of age or older.
6. Patients, 16 years or older, must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
7. If patients are childbearing or have child-fathering potential, they must use barrier contraception during intercourse while being treated on this study.
8. Bone marrow function: absolute neutrophil count (ANC) 1,000/ul; platelets 75,000/l.
9. Renal function: creatinine 2.0 x institutional upper limit of normal (ULN).
10. Hepatic function: bilirubin 2.5 x ULN; AST 5.0 x ULN.
11. Patients must have received at least one systemic chemotherapy treatment or else refuse to be treated with cytotoxic therapy.
12. Twenty-eight days or more should have elapsed since the patient has received any prior systemic therapy.
13. Patients must have documented symptomatic or radiologic progression to their preceding therapy.
14. For patients treated with prior radiation, 21 days or more should have elapsed since the administration of the last fraction of radiation therapy and patients must have recovered from all associated toxicities.
15. Patients must have measurable disease. The measurable lesion should be outside previously irradiated fields or have documented progression at least 6 weeks after completion of radiation.

Exclusion Criteria:

Any of the following criteria will make the patient ineligible to participate in this study:

1. Acute hepatitis or known HIV.
2. Active or uncontrolled infection.
3. Significant history of uncontrolled cardiac disease i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
4. Prior therapy which specifically and directly targets the EGFR pathway.
5. Prior severe infusion reaction to a monoclonal antibody.
6. Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
7. Other active systemic malignancy within the past year.

Primary outcomes:
measure: Number of Patients With Sarcoma Who Are Tumor Progression Free and Alive at Four Months From Start of Treatment With Single-agent Cetuximab.
timeFrame: 4 months
Secondary outcomes:
measure: Progression Free Survival.
timeFrame: survival
measure: Overall Survival
timeFrame: months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: Rashmi Chugh, M.D.
role: PRINCIPAL_INVESTIGATOR
References: