Clinical trial NCT00122473: Imatinib in Dermatofibrosarcoma Protuberans (DFSP)
Official title: Open-label Trial of Glivec® (Imatinib Mesylate) in Patients With Primary or Recurrent Dermatofibrosarcoma Protuberans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Dermatofibrosarcoma
Keywords: Dermatofibrosarcoma
Imatinib
Tyrosine Kinase Inhibitor
Lead sponsor: Dermatologic Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2005-07-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether imatinib is effective in the treatment of primary and recurrent dermatofibrosarcoma protuberans (DFSP).

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.

Eligibility 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

Primary outcomes:
measure: Tumor response at 6 and 12 weeks
Secondary outcomes:
measure: Rate of relapse within the first 2 years
measure: Association of tumor response with cytogenetic and receptor expression status
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Skin Cancer Unit, German Cancer Research Center and Department of Dermatology, University Hospital of Mannheim
state: Baden-Württemberg
city: Buxtehude
country: Germany
facility: Department of Dermatology, ElbeKliniken - Klinikum Buxtehude
state: Niedersachsen
city: Homburg/Saar
country: Germany
facility: Department of Dermatology, The Saarland University Hospital
state: Saarland
city: Halle/Saale
country: Germany
facility: Department of Dermatology, Martin-Luther-University Halle-Wittenberg
state: Sachsen-Anhalt
Study officials:
affiliation: Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany
name: Selma Ugurel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany
name: Dirk Schadendorf, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1200/JCO.2005.07.088.
citation: 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. doi: 10.1097/00001813-200504000-00014.
citation: 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. doi: 10.1002/pbc.20249.
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citation: 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. doi: 10.1002/gcc.10202.
citation: 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. doi: 10.1002/ijc.10535.
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citation: 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.
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citation: 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.