RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblastoma.

Condition	Treatment or Intervention	Phase
recurrent adult soft tissue sarcoma stage III adult soft tissue sarcoma stage IV adult soft tissue sarcoma adult fibrosarcoma adult malignant fibrous histiocytoma	Drug: imatinib mesylate  Procedure: conventional surgery  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the therapeutic activity of imatinib mesylate in patients with locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblastoma.
• Determine the progression-free rate at 14 weeks in patients treated with this drug.

Secondary

• Determine objective response rate, progression-free survival, and overall survival in patients treated with this drug.
• Determine the duration of response in patients treated with this drug.

OUTLINE: This is an open-label, non-randomized, multicenter study.

Patients receive oral imatinib mesylate twice daily for at least 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 14 weeks receive imatinib mesylate for 12 additional weeks. Patients with a partial or complete response at 14 weeks undergo surgical resection if possible. If surgical resection of all remaining tumor is not possible OR if complete resection is not achieved (section margins positive), patients continue to receive imatinib mesylate in the absence of disease progression

Patients are followed monthly for 6 months, every 3 months for 6 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed dermatofibrosarcoma protuberans or giant cell fibroblastoma
• Locally advanced or metastatic disease
• Measurable disease
• Not amenable to surgery, radiotherapy, or combined modality therapy with curative intent
• Documented progressive disease within the past 3 months
• Previously irradiated lesions must show disease progression
• Tumor expressing COL1A1/PDGF-beta by fluorescence in situ hybridization
• Translocation t(17;22)(q22;q13)
• No prior chemotherapy OR previously treated with 1, and only 1, line of combination chemotherapy with ifosfamide and doxorubicin OR 2 lines of single-agent therapy OR relapsed within 6 months after adjuvant chemotherapy

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 mg/dL* NOTE: *Transfusion allowed

Hepatic

• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present)
• Bilirubin ≤ 1.5 times ULN
• No uncontrolled hepatic disease

Renal

• Creatinine ≤ 1.5 times ULN
• No uncontrolled renal disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• HIV negative
• No uncontrolled diabetes
• No active or uncontrolled infection
• No concurrent severe or uncontrolled medical disease
• No medical, psychological, familial, sociological, or geographical condition that would preclude study participation, compliance, or giving informed consent
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 28 days since prior biologic therapy
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent anticancer biologic agents

Chemotherapy

• See Disease Characteristics
• More than 28 days since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 6 months since prior radiotherapy
• No concurrent radiotherapy
• Concurrent palliative radiotherapy allowed provided radiotherapy will not be administered to a target lesion

Surgery

• Not specified

Other

• More than 28 days since prior investigational drugs
• No concurrent therapeutic anticoagulation therapy with warfarin
• Concurrent low-molecular weight heparin or mini-dose warfarin for prophylaxis of central venous catheter thrombosis allowed
• No other concurrent anticancer agents
• No other concurrent investigational drugs
• No other concurrent cytostatic agents
• No other concurrent tyrosine kinase inhibitors

Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands; Recruiting

Study chairs or principal investigators

Allan T. van Oosterom, MD, PhD,  U.Z. Gasthuisberg   

Study ID Numbers:  CDR0000370799; EORTC-62027; NCT00085475; EUDRACT-2004-002538-20
Record last reviewed:  March 2005
Last Updated:  March 15, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085475
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08