Phase II Study of Glivec (Imatinib) in Locally Advanced and/or Metastatic Soft Tissue Sarcomas Expressing the t(17;22)(q22;q13) Translocation Resulting in a COL1A1/PDGF-beta Fusion Protein i.e. DermatoFibroSarcoma Protuberans (DFSP) and Giant Cell Fibroblastoma (GCF)
18 Years
N/A
Both
Sarcoma
Trial Information
Phase II Study of Glivec (Imatinib) in Locally Advanced and/or Metastatic Soft Tissue Sarcomas Expressing the t(17;22)(q22;q13) Translocation Resulting in a COL1A1/PDGF-beta Fusion Protein i.e. DermatoFibroSarcoma Protuberans (DFSP) and Giant Cell Fibroblastoma (GCF)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free rate at 14 weeks
Safety Issue:
No
Principal Investigator
Allan T. van Oosterom, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
U.Z. Gasthuisberg
Authority:
United States: Federal Government
Study ID:
EORTC-62027
NCT ID:
NCT00085475
Start Date:
April 2004
Completion Date:
Related Keywords:
- Sarcoma
- recurrent adult soft tissue sarcoma
- stage III adult soft tissue sarcoma
- stage IV adult soft tissue sarcoma
- adult fibrosarcoma
- adult malignant fibrous histiocytoma
- Dermatofibrosarcoma
- Sarcoma
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