Trial of Cetuximab in Patients With Metastatic and/or Locally Advanced Soft Tissue and Bony Sarcomas

January 15, 2013 updated by: University of Michigan Rogel Cancer Center

Phase II Trial of Cetuximab in Patients With Metastatic and/or Locally Advanced Soft Tissue and Bony Sarcomas

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2

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

    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center

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

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

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: EGFR positive
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
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.
Cetuximab 400 mg/m2 over 120 min IV initial does followed by weekly Cetuximab 250 mg/m2 over 60 min
Active Comparator: EGFR Negative
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
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.
Cetuximab 400 mg/m2 over 120 min IV initial does followed by weekly Cetuximab 250 mg/m2 over 60 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Sarcoma Who Are Tumor Progression Free and Alive at Four Months From Start of Treatment With Single-agent Cetuximab.
Time Frame: 4 months
Time of cetuximab administration to clinically documented progression of disease or death assessed for four months after starting cetuximab therapy
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival.
Time Frame: survival
Time of cetuximab administration to clinically documented progression of disease or death assessed for four months
survival
Overall Survival
Time Frame: months
Time of cetuximab administration to clinically documented death assessed for four months
months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Rashmi Chugh, M.D., University of Michigan

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

June 1, 2005

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

September 2, 2005

First Submitted That Met QC Criteria

September 6, 2005

First Posted (Estimate)

September 7, 2005

Study Record Updates

Last Update Posted (Estimate)

January 24, 2013

Last Update Submitted That Met QC Criteria

January 15, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Other Study ID Numbers

  • UMCC 2004-078
  • Legacy IRB #2005-0072 (Other Identifier: University of Michigan Medical IRB)

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.

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