Trial Background

Imatinib (commonly known as Gleevec) is a drug currently used to treat different types of leukemia, gastrointestinal stromal tumors, and a rare condition called systemic mastocytosis.  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 laboratory studies, imatinib inhibits cell growth and division and induces cell death 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 tumor of connective tissue that arises in the dermis (the inner layer of the two main layers of tissue that make up the skin).  Complete surgical excision is the standard treatment but is usually extensive and may result in loss of function in a limb or disfigurement.

Treatment of DFSP with imatinib mesylate is a rational therapy for this rare disease that targets transduction of these growth signals that are crucial for the characteristic behavior 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 inhibiting activation of the PDGF receptor.

Trial

The purpose of this study is to examine the effect of imatinib on dermatofibrosarcoma protuberan tumors.  More specifically, its purpose is to study the molecular events that occur upon treatment with imatinib, to reveal the mechanism of antitumor activity and also uncover the mechanisms in the cell that cause some tumors to be resistant this medication.  This trial will study the effects of imatinib on the growth and death processes of the DFSP tumor cells to learn if it may be a good treatment for patients with DFSP whom cannot undergo surgery or are not cured by surgery.

Imatinib will be taken for a period of time before the date that the surgery is scheduled to remove the tumor.  On the day of surgery, imatinib should be taken again.

Up to 15-20 patients will be recruited to this study from across the country.

Participation in the trial

To be eligible to participate in this trial a patient must:

1.      Be 18 years of age or older

2.      Have a suspected or documented diagnosis of DFS

3.      Be able to undergo surgical resection of the DFSP

4.      Have at least one site of measurable disease

5.      Be able to carry out work of a light or sedentary nature, e.g., light housework, office work and may still be able to participate if he/she is restricted in physically strenuous activity

6.      Have adequate organ function and laboratory studies within normal range

You will have blood tests, a physical exam, and scans before you are enrolled and your test results must be within the limits outlined for eligibility to participate in the study protocol.

The following will NOT be able to participate:

1.      Patients who will receive radiation therapy to the site of DFSP prior to resection.

2.      Patients with heart problems

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

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

*this represents only a partial list of requirements to be included or excluded from the study.  A complete list is available from SARC or Dr. Schuetze.

For more information contact SARC at 734.930.7600 or Dr. Schuetze at 734.936.0453.

This trial is registered at clinicaltrials.gov and can be found at:

http://www.clinicaltrials.gov/ct/show/NCT00243191?order=4

The full title is: Study of a Short Course of Neoadjuvant Gleevec (Imatinib Mesylate) in Dermatofibrosarcoma Protuberans (SARC004)

Glossary:

*Excision: Removal by surgery

*GIST: Gastrointestinal stromal tumor. A type of tumor that usually begins in cells in the wall of the gastrointestinal tract. It can be benign or malignant. Also called gastrointestinal stromal tumor.

*Leukemia: Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

*Neoadjuvant therapy: Treatment given before surgery.

*Platelet-derived growth factor (PDGF):  One of many growth factors (proteins) that regulate cell growth and division.

*Stem cell factor (SCF): A protein that has important roles in the proliferation and differentiation of certain types of cells.

*Systemic mastocytosis: A rare disease in which too many mast cells (a type of immune system cell) are found in the skin, bones, joints, lymph nodes, liver, spleen, and gastrointestinal tract. Mast cells give off chemicals such as histamine that can cause flushing (a hot, red face), itching, abdominal cramps, muscle pain, nausea, vomiting, diarrhea, low blood pressure, and shock.