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Imatinib Mesylate in Treating Patients With Locally Recurrent or Metastatic Dermatofibrosarcoma Protuberans

Primary Purpose

Adult Fibrosarcoma, Dermatofibrosarcoma Protuberans, Recurrent Adult Soft Tissue Sarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
imatinib mesylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Fibrosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 Platelets >= 100,000/uL Serum bilirubin =< 1.5 x institutional upper limit of normal (IULN) Serum transaminase (SGOT or SGPT) must be =< 2.5 x IULN Serum albumin must be >= 2.5 mg/dl Patients must not be taking therapeutic doses of coumadin (Warfarin) at the time of registration; patients requiring therapeutic anticoagulation may use heparin, low molecular weight heparin or other agents; mini-dose coumadin (1 mg orally every day as prophylaxis is allowed Patients with known CNS metastases are not eligible Pregnant or nursing women may not participate on this study; there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with imatinib; male/female patients of reproductive potential must also agree to employ an effective contraceptive barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patients registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study have been entered into the database

Sites / Locations

  • Southwest Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (imatinib mesylate)

Arm Description

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.

Outcomes

Primary Outcome Measures

Response rate (confirmed complete and confirmed partial response)
Progression-free survival
Frequency and severity of toxicity as assessed by NCI CTCAE version 3.0
Relationship between PDGFB and survival

Secondary Outcome Measures

Relationship between PDGFB and tumor response to imatinib mesylate

Full Information

First Posted
June 10, 2004
Last Updated
February 27, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00084630
Brief Title
Imatinib Mesylate in Treating Patients With Locally Recurrent or Metastatic Dermatofibrosarcoma Protuberans
Official Title
A Phase II Study of Imatinib (NSC-716051) in Patients With Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Fibrosarcoma, Dermatofibrosarcoma Protuberans, Recurrent Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (imatinib mesylate)
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
imatinib mesylate
Other Intervention Name(s)
CGP 57148, Gleevec, Glivec
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response rate (confirmed complete and confirmed partial response)
Time Frame
Up to 5 years
Title
Progression-free survival
Time Frame
At 1 year
Title
Frequency and severity of toxicity as assessed by NCI CTCAE version 3.0
Time Frame
Up to 5 years after completion of treatment
Title
Relationship between PDGFB and survival
Time Frame
At baseline and at the time of progression
Secondary Outcome Measure Information:
Title
Relationship between PDGFB and tumor response to imatinib mesylate
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 Platelets >= 100,000/uL Serum bilirubin =< 1.5 x institutional upper limit of normal (IULN) Serum transaminase (SGOT or SGPT) must be =< 2.5 x IULN Serum albumin must be >= 2.5 mg/dl Patients must not be taking therapeutic doses of coumadin (Warfarin) at the time of registration; patients requiring therapeutic anticoagulation may use heparin, low molecular weight heparin or other agents; mini-dose coumadin (1 mg orally every day as prophylaxis is allowed Patients with known CNS metastases are not eligible Pregnant or nursing women may not participate on this study; there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with imatinib; male/female patients of reproductive potential must also agree to employ an effective contraceptive barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines At the time of patients registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study have been entered into the database
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Schuetze
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southwest Oncology Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78245
Country
United States

12. IPD Sharing Statement

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Imatinib Mesylate in Treating Patients With Locally Recurrent or Metastatic Dermatofibrosarcoma Protuberans

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