Sarcoma
Conditions
Keywords
Unresectable/metastatic high grade soft tissue bony sarcoma
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.
Interventions
DRUGCetuximab
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.
Sponsors
Bristol-Myers Squibb
Eli Lilly and Company
University of Michigan Rogel Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Sarcoma Who Are Tumor Progression Free and Alive at Four Months From Start of Treatment With Single-agent Cetuximab. | 4 months | Time of cetuximab administration to clinically documented progression of disease or death assessed for four months after starting cetuximab therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival. | survival | Time of cetuximab administration to clinically documented progression of disease or death assessed for four months |
| Overall Survival | months | Time of cetuximab administration to clinically documented death assessed for four months |
Countries
United States
Participant flow
Recruitment details
36 subjects were recruited between June of 2005 and June of 2008 in the Comprehensive Cancer Center outpatient Oncology Clinics at the University of Michigan Health Systems
Pre-assignment details
Potential participants who appeared to meet study criteria were approached with a brief discussion of the study. If interested, a more in - depth detail discussion of the risks and benefits of potentially participating in the study took place with the subject as well as any family members that may have been present.
Participants by arm
| Arm | Count |
|---|---|
| Epidermal Growth Factor Receptor Negative Sarcoma does not express Epidermal growth factor receptor. Patients received cetuximab 400 mg per meter squared IV followed by 250 mg per meter squared weekly | 15 |
| Epidermal Growth Factor Receptor Positive Sarcoma expresses Epidermal growth factor receptor. Patients received cetuximab 400 mg per meter squared IV followed by 250 mg per meter squared weekly | 21 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 10 | 18 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Epidermal Growth Factor Receptor Positive | Epidermal Growth Factor Receptor Negative | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 14 Participants | 31 Participants |
| Age Continuous | 54 years FULL_RANGE 2 | 49 years FULL_RANGE 2 | 54 years FULL_RANGE 2 |
| Region of Enrollment United States | 21 participants | 15 participants | 36 participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 14 Participants | 5 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 15 | 11 / 21 |
| serious Total, serious adverse events | 9 / 15 | 10 / 21 |
Outcome results
Primary
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
Time frame: 4 months
Population: per protocol all patients that received drug were evaluated for the primary endpoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epidermal Growth Factor Receptor Negative | Number of Patients With Sarcoma Who Are Tumor Progression Free and Alive at Four Months From Start of Treatment With Single-agent Cetuximab. | 3 participants |
| Epidermal Growth Factor Receptor Positive | Number of Patients With Sarcoma Who Are Tumor Progression Free and Alive at Four Months From Start of Treatment With Single-agent Cetuximab. | 1 participants |
Comparison: Estimate a 4 month progression-free survival rate for each group.p-value: <0.05Fisher Exact
Secondary
Overall Survival
Time of cetuximab administration to clinically documented death assessed for four months
Time frame: months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epidermal Growth Factor Receptor Negative | Overall Survival | 15.7 months |
| Epidermal Growth Factor Receptor Positive | Overall Survival | 7.7 months |
Secondary
Progression Free Survival.
Time of cetuximab administration to clinically documented progression of disease or death assessed for four months
Time frame: survival
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epidermal Growth Factor Receptor Negative | Progression Free Survival. | 1.8 months |
| Epidermal Growth Factor Receptor Positive | Progression Free Survival. | 1.7 months |