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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00245102
First Posted: October 27, 2005
Last Update Posted: May 23, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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.

Condition Intervention Phase
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 Drug: sorafenib tosylate Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Study of Sorafenib (BAY43-9006) in Non-GIST Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Response Rate Measured by Complete Response (CR) Rate and Partial Response (PR) Rate as Determined by RECIST [ Time Frame: Up to 4 weeks ]
    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.


Enrollment: 147
Study Start Date: September 2005
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00245102


Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Robert Maki Memorial Sloan Kettering Cancer Center
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00245102     History of Changes
Other Study ID Numbers: NCI-2012-01469
NCI-2012-01469 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-7060
CDR0000449962
MSKCC-05081
05-081 ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
7060 ( Other Identifier: CTEP )
N01CM62206 ( U.S. NIH Grant/Contract )
P30CA008748 ( U.S. NIH Grant/Contract )
N01CM62201 ( U.S. NIH Grant/Contract )
First Submitted: October 25, 2005
First Posted: October 27, 2005
Results First Submitted: November 19, 2013
Results First Posted: January 20, 2014
Last Update Posted: May 23, 2014
Last Verified: December 2012

Additional relevant MeSH terms:
Sarcoma
Leiomyosarcoma
Sarcoma, Synovial
Carcinosarcoma
Mixed Tumor, Mullerian
Hemangiosarcoma
Histiocytoma
Histiocytoma, Benign Fibrous
Histiocytoma, Malignant Fibrous
Neurofibrosarcoma
Uterine Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Connective Tissue
Neoplasms, Complex and Mixed
Neoplasms, Vascular Tissue
Neoplasms, Fibrous Tissue
Fibrosarcoma
Neurofibroma
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genital Neoplasms, Female
Urogenital Neoplasms