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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00245102
First received: October 25, 2005
Last updated: December 13, 2012
Last verified: December 2012
History of Changes
  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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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:

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]
    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:
  • Progression-free survival rate (CR, PR, and SD) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Will be estimated and a confidence interval provided. Kaplan-Meier curves for overall survival and progression free survival will be constructed for each stratum.

  • Clinical benefit rate (CR, PR, and SD) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be estimated and a confidence interval provided.

  • Overall survival [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Will be estimated and a confidence interval provided. Kaplan-Meier curves for overall survival and progression free survival will be constructed for each stratum.


Enrollment: 222
Study Start Date: September 2005
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00245102     History of Changes
Other Study ID Numbers: NCI-2012-01469, 05-081, N01CM62201, N01CM62206, CDR0000449962
Study First Received: October 25, 2005
Last Updated: December 13, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Histiocytoma
Carcinosarcoma
Mixed Tumor, Mullerian
Hemangiosarcoma
Leiomyosarcoma
Sarcoma, Synovial
Sarcoma
Histiocytoma, Benign Fibrous
Neurofibrosarcoma
Neurilemmoma
Uterine Neoplasms
Histiocytoma, Malignant Fibrous
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Neoplasms, Vascular Tissue
Neoplasms, Muscle 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
Neuroendocrine Tumors

ClinicalTrials.gov processed this record on May 19, 2013