Imatinib in Dermatofibrosarcoma Protuberans (DFSP)
Information source: Dermatologic Cooperative Oncology Group
Information obtained from ClinicalTrials.gov on December 31, 2007
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Dermatofibrosarcoma
Intervention: Imatinib (Glivec) (Drug)
Phase: Phase 1/Phase 2
Status: Active, not recruiting
Sponsored by: Dermatologic Cooperative Oncology Group
Official(s) and/or principal investigator(s):
Selma Ugurel, MD, Principal Investigator, Affiliation: Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany
Dirk Schadendorf, MD, Principal Investigator, Affiliation: Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany
The purpose of this study is to determine whether imatinib is effective in the treatment of
primary and recurrent dermatofibrosarcoma protuberans (DFSP).
Official title: Open-Label Trial of Glivec« (Imatinib Mesylate) in Patients With Primary or Recurrent Dermatofibrosarcoma Protuberans
Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary outcome: Tumor response at 6 and 12 weeks
Rate of relapse within the first 2 years
Association of tumor response with cytogenetic and receptor expression status
This study is aimed to investigate the efficacy of imatinib (Glivec) in the treatment of
primary and locally relapsed dermatofibrosarcoma protuberans (DFSP). DFSP is a cutaneous
neoplasm well known for its overexpression of the platelet-derived growth factor (PDGF).
Herein, imatinib provides a systemic treatment option that offers the possibility of a
reduction of the wide surgical margins used today in surgery of primary DFSP, or even of a
complete avoidance of surgical treatment in this disease. Since imatinib exerts its function
via interference with protein tyrosine kinase activities, it inhibits the platelet-derived
growth factor receptor (PDGF-R) signaling cascade that plays a crucial role in the
pathogenesis and tumor growth of DFSP. Since imatinib has been shown to shrink metastatic
lesions of DFSP, there is a strong rationale to expect that it also decreases cell
proliferation and tumor growth in primary DFSP.
Minimum age: 18 Years.
Maximum age: N/A.
Histological diagnosis of primary or recurrent dermatofibrosarcoma protuberans
Measurable tumor parameters (by magnetic resonance imaging [MRI])
Patient >/= 18 years of age
ECOG performance status < 3
Adequate organ function
Patients must be able to swallow capsules
Female patients of childbearing potential must have negative pregnancy test
Written, voluntary, informed consent; must include investigational use of tumor tissue
Any evidence of distant metastases
Patient has received any other investigational agents within 28 days of first day of study
Patient is < 5 years free of another primary malignancy except basal cell skin cancer or
cervical carcinoma in situ
Grade III/IV cardiac problems as defined by the New York Heart Association
Severe and/or uncontrolled medical disease
Known diagnosis of human immunodeficiency virus (HIV) infection
Locations and Contacts
Skin Cancer Unit, German Cancer Research Center and Department of Dermatology, University Hospital of Mannheim, Mannheim, Baden-W├╝rttemberg 68167, Germany
Department of Dermatology, ElbeKliniken - Klinikum Buxtehude, Buxtehude, Niedersachsen 21614, Germany
Department of Dermatology, The Saarland University Hospital, Homburg/Saar, Saarland 66424, Germany
Department of Dermatology, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Sachsen-Anhalt 06097, Germany
McArthur GA, Demetri GD, van Oosterom A, Heinrich MC, Debiec-Rychter M, Corless CL, Nikolova Z, Dimitrijevic S, Fletcher JA. Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol. 2005 Feb 1;23(4):866-73.
Labropoulos SV, Fletcher JA, Oliveira AM, Papadopoulos S, Razis ED. Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate. Anticancer Drugs. 2005 Apr;16(4):461-6.
Price VE, Fletcher JA, Zielenska M, Cole W, Viero S, Manson DE, Stuart M, Pappo AS. Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans. Pediatr Blood Cancer. 2005 May;44(5):511-5.
Mizutani K, Tamada Y, Hara K, Tsuzuki T, Saeki H, Tamaki K, Matsumoto Y. Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans. Br J Dermatol. 2004 Jul;151(1):235-7. Review. No abstract available.
McArthur G. Molecularly targeted treatment for dermatofibrosarcoma protuberans. Semin Oncol. 2004 Apr;31(2 Suppl 6):30-6. Review.
Sirvent N, Maire G, Pedeutour F. Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer. 2003 May;37(1):1-19. Review.
Maki RG, Awan RA, Dixon RH, Jhanwar S, Antonescu CR. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int J Cancer. 2002 Aug 20;100(6):623-6.
Rubin BP, Schuetze SM, Eary JF, Norwood TH, Mirza S, Conrad EU, Bruckner JD. Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans. J Clin Oncol. 2002 Sep 1;20(17):3586-91.
Sjoblom T, Shimizu A, O'Brien KP, Pietras K, Dal Cin P, Buchdunger E, Dumanski JP, Ostman A, Heldin CH. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res. 2001 Aug 1;61(15):5778-83.
Greco A, Roccato E, Miranda C, Cleris L, Formelli F, Pierotti MA. Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer. 2001 May 1;92(3):354-60.
Shimizu A, O'Brien KP, Sjoblom T, Pietras K, Buchdunger E, Collins VP, Heldin CH, Dumanski JP, Ostman A. The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res. 1999 Aug 1;59(15):3719-23.
Starting date: January 2004
Ending date: January 2007
Last updated: September 11, 2006