Imatinib in Dermatofibrosarcoma Protuberans (DFSP)

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

Secondary outcome:

Rate of relapse within the first 2 years

Association of tumor response with cytogenetic and receptor expression status

Detailed description: 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. Gender(s): Both.

Criteria:

Inclusion Criteria: 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 biopsies. Exclusion Criteria: Any evidence of distant metastases Patient has received any other investigational agents within 28 days of first day of study drug dosing 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

Skin Cancer Unit, German Cancer Research Center and Department of Dermatology, University Hospital of Mannheim, Mannheim, Baden-Württemberg 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

Related publications:

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