Expired Study
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Ann Arbor, Michigan 48109


Purpose:

This research study is for patients who have been diagnosed with a rare type of tissue tumor (DFSP). Surgery has been recommended to treat this cancer. Surgery cures most patients of dermatofibrosarcoma protuberans (DFMP), but the tumor can grow back around the site of surgery in up to one-quarter of patients and can occasionally spread throughout the body to vital organs such as the lungs. Rarely will patients die of this disease. Gleevec (imatinib) has been prescribed to a few patients with inoperable DFSP because Gleevec can stop or block a signal that is believed to cause the tumor cells to grow. Gleevec appeared to help a few of these patients by stopping the growth of the tumor and causing the tumor cells to die. Gleevec is not approved by the FDA (Food and Drug Administration) for treatment of DFSP. This research study is to see if the use of Gleevec can be used to treat DFSP. We would like to study the effects of the Gleevec on the growth and death processes of the DFSP tumor cells to learn if Gleevec may be a good treatment for patients with DFSP whom cannot undergo surgery


Study summary:

Gleevec (imatinib mesylate) is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive (Ph+) chronic myeloid leukemia. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express activating c-kit mutations, and dermatofibrosarcoma protuberans cells which express PDGF receptors. Dermatofibrosarcoma protuberans (DFSP) is a rare, highly invasive, low grade, fibroblastic neoplasm that arises in the dermis and subcutis in adults. Complete surgical excision by wide resection is the standard treatment but may result in cosmetic disfigurement or functional impairment. Local recurrence of disease develops in approximately 25% of patients within 5 years of surgery [Bowne, 2000]. The optimal treatment of unresectable or recurrent DFSP is not well defined. The critical pathogenic event in DFSP is chromosomal translocation of the gene encoding the platelet-derived growth factor beta chain. The most common partner is the gene encoding the collagen type 1 alpha 1 chain. Aberrant expression of the COL1A1-PDGFB chimeric gene results in production of functional platelet-derived growth factor that can bind to and activate platelet-derived growth factor receptors on tumor cells providing an autocrine and/or paracrine mitogenic stimulus [Shimizu, 1999; Simon, 2001]. Reports on the use of imatinib mesylate to treat unresectable DFSP have demonstrated significant antitumor activity in 2 of 3 patients [Maki, 2002, Rubin 2002]. In one patient who had resection of the residual tumor after 4 months of therapy with imatinib mesylate, a complete histologic response was seen [Rubin 2002]. Response of DFSP to imatinib in single patient studies has been reported by others. The objective response rate of DFSP to imatinib is under investigation in a larger cohort of patients with metastatic or unresectable disease but molecular changes will not be studied. Treatment of DFSP with imatinib mesylate is a rational therapy for this rare disease that targets transduction of a growth signal that appears to be crucial for the growth and viability of tumor cells. The mechanism of antitumor activity of imatinib in DFSP has not been studied in detail but is presumed to be mediated by inhibition of phosphorylation of the platelet-derived growth factor receptor. Further study of the molecular events that occur in DFSP upon treatment with imatinib is needed to help elucidate the mechanism of antitumor activity and potential mechanisms of tumor resistance to treatment with imatinib. Additional treatment strategies may become evident with a clearer understanding of the downstream effects of imatinib interacting with the PDGFB receptors in DFSP.


Criteria:

Inclusion criteria 1. Patients 18 years of age or older. 2. Suspected or documented diagnosis of dermatofibrosarcoma protuberans (DFSP). Patients with suspected diagnosis of DSFP must have DFSP confirmed by pathology at the local institution prior to dispensing and the start of imatinib. 3. Patient is medically able to undergo surgical resection of the DFSP and resection of the DFSP is recommended for clinical management of the disease. 4. Patient has at least one site of measurable (macroscopic) disease. 5. Performance status 0, 1 or 2 (ECOG) (see Section 7.1). 6. Adequate end organ function, defined as the following: - Total bilirubin < 1.5 x institutional upper limit of normal (ULN) - SGOT and SGPT < 2.5 x UNL - Creatinine < 1.5 x ULN A - Absolute neutrophil count > 1.5 x 109/L - Platelets > 100 x 109/L. 7. Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. 8. Written, voluntary informed consent. Exclusion criteria 1. Patients who will receive radiation therapy to the site of DFSP prior to resection. 2. Patients with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study). 3. Female patients who are pregnant or breast-feeding. 4. Patients who have a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection) that may worsen because of imatinib. 5. Patients who have known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis). 6. Patients who have a known diagnosis of human immunodeficiency virus (HIV) infection. 7. Patients who have received chemotherapy within 4 weeks prior to study entry. 8. Patients who have had a major surgery within 2 weeks prior to study entry. Incisional biopsy or partial excision of dermatofibrosarcoma protuberans to establish the diagnosis and/or to collect pretreatment tumor tissue does not qualify as major surgery.


Study is Available At:


Original ID:

UMCC 2005-002


NCT ID:

NCT00176709


Secondary ID:

Legacy IRB #2005-174


Study Acronym:


Brief Title:

A Short Course of Neoadjuvant Gleevec (Imatinib Mesylate) in Dermatofibrosarcoma Protuberans


Official Title:

Study of a Short Course of Neoadjuvant Gleevec (Imatinib Mesylate) in Dermatofibrosarcoma Protuberans


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Michigan Cancer Center


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Intervention Model:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

20


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Scott Schuetze, M.D.,PhD
Principal Investigator
University of Michigan Cancer Center

Study Dates

Start Date:September 2005
Completion Date:March 2010
Completion Type:Actual
Primary Completion Date:November 2008
Primary Completion Type:Actual
Verification Date:March 2011
Last Changed Date:March 22, 2011
First Received Date:September 9, 2005

Study Outcomes

Outcome Type:Primary Outcome
Measure:response
Time Frame:3 months
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:toxicity
Time Frame:2 months
Safety Issues:True

Study Interventions

Intervention Type:Drug
Name:Gleevec

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Michigan Cancer Center

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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