Imatinib in Dermatofibrosarcoma Protuberans (DFSP)

Dermatofibrosarcoma Clinical Trial

Official title:

Open-label Trial of Glivec® (Imatinib Mesylate) in Patients With Primary or Recurrent Dermatofibrosarcoma Protuberans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00122473
• Other study ID #: ADO/VOD DFSP 001
• Secondary ID: CSTI571BDE25
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 20, 2005
• Last updated: July 28, 2011
• Start date: January 2004
• Est. completion date: January 2007

Study information

• Verified date: July 2011
• Source: Dermatologic Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dermatofibrosarcoma

Intervention

Drug:
• Imatinib (Glivec)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Dermatologic Cooperative Oncology Group

Country where clinical trial is conducted

Germany, 

References & Publications (11)

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. — View 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. — View 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. — View Citation

McArthur G. Molecularly targeted treatment for dermatofibrosarcoma protuberans. Semin Oncol. 2004 Apr;31(2 Suppl 6):30-6. Review. — View 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. — View Citation

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. — View 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. — View Citation

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. — View Citation

Shimizu A, O'Brien KP, Sjöblom 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. — View 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. Review. — View Citation

Sjöblom 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response at 6 and 12 weeks
Secondary	Rate of relapse within the first 2 years
Secondary	Association of tumor response with cytogenetic and receptor expression status