A Phase II Study of Imatinib (NSC-716051) in Patients With Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans
Overview
- Phase
- Phase 2
- Intervention
- imatinib mesylate
- Conditions
- Adult Fibrosarcoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Response rate (confirmed complete and confirmed partial response)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This phase II trial is studying how well imatinib mesylate works in treating patients with locally recurrent or metastatic dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP (a type of soft tissue sarcoma). Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth
Detailed Description
PRIMARY OBJECTIVES: I. To assess the response rate (confirmed complete and confirmed partial response) in patients with locally advanced or metastatic dermatofibrosarcoma protuberans (DFSP) treated with imatinib. II. To estimate the one-year progression-free survival probability in this population when treated with imatinib. III. To evaluate the frequency and severity of toxicities associated with this treatment. IV. To measure the presence of PDGFB gene rearrangement in DFSP detectable by RT-PCR (for COL1A1-PDGFB fusions) and/or FISH (PDGFB rearrangements with unknown partners) and explore relationships between these measures and survival and tumor response in a preliminary manner. V. To investigate in a preliminary fashion the correlation of plasma levels of imatinib after 1 month of treatment with the response of DFSP. VI. To obtain tumor material for additional future correlative studies of the activity of intracellular kinases, cDNA microarray analyses and PDGFB receptor gene sequence analyses. OUTLINE: Patients receive oral imatinib mesylate once daily on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with documented tumor progression and no serious side effects may continue therapy at a higher dose for another 6 courses. Patients are followed every 6 months for 2 years and then annually for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed diagnosis of either dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP; patients with transformed fibrosarcomatous DFSP may have primary, locally recurrent or metastatic disease; patients with DFSP must have locally recurrent or metastatic disease OR primary disease for which complete excision with a wide margin (\> 1-2 cm) would result in unacceptable cosmetic disfigurement or functional impairment
- •Patients must have measurable disease; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed
- •Pathology materials must be submitted for review; failure to submit pathology materials will render the patient ineligible
- •Patients must be willing to have blood samples submitted for testing of drug levels; also, it is strongly recommended that patients submit fresh/frozen tumor tissue that will yield 0.5 grams (0.5 cubic centimeters) for molecular correlative studies related to the PDGFR pathway
- •Patient must not have had chemotherapy, biologic therapy or investigational agents for this tumor within 28 days prior to registration
- •Patients may have received prior major surgery for this disease; at least 14 days must have elapsed since the surgery and the patient must have recovered from all side effects associated with surgery; biopsy of dermatofibrosarcoma protuberans is not considered major surgery and a 14-day delay after biopsy is not required
- •Prior radiotherapy is allowed, provided at least four weeks have elapsed since the last treatment, there is evidence of progressive disease within or measurable disease outside of the radiation field, and the patient must have recovered from all associated toxicities at the time of registration
- •Patients must have Zubrod performance status of =\< 2
- •WBC \>= 2,000/uL
- •ANC \>= 1,500/uL
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate once daily on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with documented tumor progression and no serious side effects may continue therapy at a higher dose for another 6 courses.
Intervention: imatinib mesylate
Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate once daily on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with documented tumor progression and no serious side effects may continue therapy at a higher dose for another 6 courses.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Response rate (confirmed complete and confirmed partial response)
Time Frame: Up to 5 years
Progression-free survival
Time Frame: At 1 year
Frequency and severity of toxicity as assessed by NCI CTCAE version 3.0
Time Frame: Up to 5 years after completion of treatment
Relationship between PDGFB and survival
Time Frame: At baseline and at the time of progression
Secondary Outcomes
- Relationship between PDGFB and tumor response to imatinib mesylate(Up to 5 years)