Imatinib in Dermatofibrosarcoma Protuberans (DFSP) - Full Text View

Purpose

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

Condition	Intervention	Phase
Dermatofibrosarcoma	Drug: Imatinib (Glivec)	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Open-label Trial of Glivec® (Imatinib Mesylate) in Patients With Primary or Recurrent Dermatofibrosarcoma Protuberans

Resource links provided by NLM:

Genetics Home Reference related topics: dermatofibrosarcoma protuberans

MedlinePlus related topics: Cancer

Drug Information available for: Imatinib Imatinib mesylate

U.S. FDA Resources

Further study details as provided by Dermatologic Cooperative Oncology Group:

Primary Outcome Measures:

Tumor response at 6 and 12 weeks

Secondary Outcome Measures:

Rate of relapse within the first 2 years
Association of tumor response with cytogenetic and receptor expression status

Estimated Enrollment:	30
Study Start Date:	January 2004
Estimated Study Completion Date:	January 2007

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00122473

Locations

Germany
Skin Cancer Unit, German Cancer Research Center and Department of Dermatology, University Hospital of Mannheim
Mannheim, Baden-Württemberg, Germany, 68167
Department of Dermatology, ElbeKliniken - Klinikum Buxtehude
Buxtehude, Niedersachsen, Germany, 21614
Department of Dermatology, The Saarland University Hospital
Homburg/Saar, Saarland, Germany, 66424
Department of Dermatology, Martin-Luther-University Halle-Wittenberg
Halle/Saale, Sachsen-Anhalt, Germany, 06097

Sponsors and Collaborators

Dermatologic Cooperative Oncology Group

Investigators

Principal Investigator:	Selma Ugurel, MD	Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany
Principal Investigator:	Dirk Schadendorf, MD	Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany

More Information

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.

ClinicalTrials.gov Identifier:	NCT00122473 History of Changes
Other Study ID Numbers:	ADO/VOD DFSP 001, CSTI571BDE25
Study First Received:	July 20, 2005
Last Updated:	July 28, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Dermatologic Cooperative Oncology Group:

Dermatofibrosarcoma
Imatinib
Tyrosine Kinase Inhibitor

Additional relevant MeSH terms:

Dermatofibrosarcoma
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma

Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013