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Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma

Primary Purpose

Adult Angiosarcoma, Adult Epithelioid Sarcoma, Adult Leiomyosarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
sorafenib tosylate
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Angiosarcoma

Eligibility Criteria

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

Inclusion Criteria: Histologically or cytologically confirmed sarcoma, including any of the following neoplastic subtypes: Giant hemangioma Angiosarcoma (including epithelioid hemangioendothelioma) Malignant peripheral nerve sheath tumor Leiomyosarcoma (closed to accrual as of 11/29/06) High-grade undifferentiated pleomorphic sarcoma (i.e., malignant fibrous histiocytoma [including myxofibrosarcoma]) (closed to accrual as of 11/29/06) Synovial sarcoma (closed to accrual as of 11/29/06) Carcinosarcoma (closed to accrual as of 11/29/06) Metastatic, locally advanced, or locally recurrent disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Lesions in a previously irradiated area may be considered measurable provided there is evidence of subsequent disease progression that cannot be attributed to necrosis or bleeding No gastrointestinal stromal tumor No known brain metastases Performance status - ECOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No evidence of bleeding diathesis Bilirubin ≤ 1.5 mg/dL INR ≤ 1.5 AST and ALT ≤ 2.5 times upper limit of normal Creatinine ≤ 1.5 mg/dL No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension No history of allergic reaction to compounds of similar chemical or biologic composition to sorafenib No known HIV positivity No active or ongoing infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychiatric illness or social situation that would preclude study compliance No swallowing dysfunction that would preclude the swallowing of tablets Other malignancies allowed provided sarcoma is the primary disease requiring treatment No other uncontrolled illness No more than 1 prior chemotherapy regimen for recurrent or metastatic disease (≤ 3 regimens for angiosarcoma or malignant peripheral nerve sheath tumor) Adjuvant chemotherapy completed > 1 year prior to study entry is not considered a line of prior treatment More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) At least 3 weeks since prior radiotherapy Recovered from prior antitumor therapy Alopecia allowed No prior sorafenib No prior small molecule inhibitors of MAPK signaling intermediates No concurrent therapeutic anticoagulation Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial devices allowed provided requirements for PT, INR, or PTT requirements are met No other concurrent investigational agents No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) No concurrent rifampin or Hypericum perforatum (St. John's wort)

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall Response Rate Measured by Complete Response (CR) Rate and Partial Response (PR) Rate as Determined by RECIST
A 5% response rate is considered not promising, a 20% response rate is considered promising. For each stratum, the response rate will be estimated and a confidence interval will be constructed.

Secondary Outcome Measures

Full Information

First Posted
October 25, 2005
Last Updated
May 7, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00245102
Brief Title
Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma
Official Title
A Multicenter Phase II Study of Sorafenib (BAY43-9006) in Non-GIST Sarcomas
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)

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 sorafenib works in treating patients with metastatic, locally advanced, or recurrent sarcoma. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Detailed Description
PRIMARY OBJECTIVES: I. The primary endpoint is the response rate (CR+PR) for each stratum of sarcoma patients treated with sorafenib as defined by RECIST. SECONDARY OBJECTIVES: I. Progression-free survival (defined as CR + PR + SD, assessed at 3 months or 6 months). II. Overall survival. III. Pharmacokinetics of sorafenib in this patient population (all sites will participate). IV. Frequency of B-raf mutations in the patients' sarcomas treated as part of this study and correlation with response or resistance to sorafenib (all sites will participate). V. Ras-raf kinase pathway activation in pre-treatment existing tumor specimens (paraffin section immunohistochemistry; all sites will participate). VI. At MSKCC only: Pre and post treatment specimen changes in downstream events of ras signaling, specifically inhibition of ERK phosphorylation. Only patients with angiosarcoma and MPNST will undergo biopsy (up to 10 patients). VII. At MSKCC only: Circulating Endothelial Cells (CECs), VE-cadherin levels, and soluble protein levels (VEGF, bFGF, endostatin) as a measures of angiogenesis before and after starting sorafenib therapy. OUTLINE: This is an open-label, non-randomized, multicenter study. Patients are stratified according to sarcoma histology (angiosarcoma vs malignant peripheral nerve sheath tumor vs leiomyosarcoma [closed to accrual as of 11/29/06] vs high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)(closed to accrual as of 11/29/06)] vs synovial sarcoma (closed to accrual as of 11/29/06) vs all other types of sarcoma). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed at 4 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Angiosarcoma, Adult Epithelioid Sarcoma, Adult Leiomyosarcoma, Adult Malignant Fibrous Histiocytoma, Adult Neurofibrosarcoma, Adult Synovial Sarcoma, Ovarian Sarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Uterine Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage III Uterine Sarcoma, Stage IV Adult Soft Tissue Sarcoma, Stage IV Uterine Sarcoma, Uterine Carcinosarcoma, Uterine Leiomyosarcoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
sorafenib tosylate
Other Intervention Name(s)
BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Overall Response Rate Measured by Complete Response (CR) Rate and Partial Response (PR) Rate as Determined by RECIST
Description
A 5% response rate is considered not promising, a 20% response rate is considered promising. For each stratum, the response rate will be estimated and a confidence interval will be constructed.
Time Frame
Up to 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed sarcoma, including any of the following neoplastic subtypes: Giant hemangioma Angiosarcoma (including epithelioid hemangioendothelioma) Malignant peripheral nerve sheath tumor Leiomyosarcoma (closed to accrual as of 11/29/06) High-grade undifferentiated pleomorphic sarcoma (i.e., malignant fibrous histiocytoma [including myxofibrosarcoma]) (closed to accrual as of 11/29/06) Synovial sarcoma (closed to accrual as of 11/29/06) Carcinosarcoma (closed to accrual as of 11/29/06) Metastatic, locally advanced, or locally recurrent disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Lesions in a previously irradiated area may be considered measurable provided there is evidence of subsequent disease progression that cannot be attributed to necrosis or bleeding No gastrointestinal stromal tumor No known brain metastases Performance status - ECOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No evidence of bleeding diathesis Bilirubin ≤ 1.5 mg/dL INR ≤ 1.5 AST and ALT ≤ 2.5 times upper limit of normal Creatinine ≤ 1.5 mg/dL No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension No history of allergic reaction to compounds of similar chemical or biologic composition to sorafenib No known HIV positivity No active or ongoing infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychiatric illness or social situation that would preclude study compliance No swallowing dysfunction that would preclude the swallowing of tablets Other malignancies allowed provided sarcoma is the primary disease requiring treatment No other uncontrolled illness No more than 1 prior chemotherapy regimen for recurrent or metastatic disease (≤ 3 regimens for angiosarcoma or malignant peripheral nerve sheath tumor) Adjuvant chemotherapy completed > 1 year prior to study entry is not considered a line of prior treatment More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) At least 3 weeks since prior radiotherapy Recovered from prior antitumor therapy Alopecia allowed No prior sorafenib No prior small molecule inhibitors of MAPK signaling intermediates No concurrent therapeutic anticoagulation Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial devices allowed provided requirements for PT, INR, or PTT requirements are met No other concurrent investigational agents No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) No concurrent rifampin or Hypericum perforatum (St. John's wort)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Maki
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

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Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma

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