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A Multicenter Phase II Study of Sorafenib (BAY43-9006) in Non-GIST Sarcomas

Phase 2
18 Years
Not Enrolling
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

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Trial Information

A Multicenter Phase II Study of Sorafenib (BAY43-9006) in Non-GIST Sarcomas


I. The primary endpoint is the response rate (CR+PR) for each stratum of sarcoma patients
treated with sorafenib as defined by RECIST.


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.

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

- 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)

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate measured by complete response (CR) rate and partial response (PR) rate as determined by RECIST

Outcome 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.

Outcome Time Frame:

Up to 4 weeks

Safety Issue:


Principal Investigator

Robert Maki

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2005

Completion Date:

Related Keywords:

  • 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
  • Histiocytoma
  • Carcinosarcoma
  • Mixed Tumor, Mullerian
  • Hemangiosarcoma
  • Leiomyosarcoma
  • Sarcoma, Synovial
  • Sarcoma
  • Histiocytoma, Benign Fibrous
  • Neurofibrosarcoma
  • Neurilemmoma
  • Uterine Neoplasms
  • Histiocytoma, Malignant Fibrous



Memorial Sloan Kettering Cancer CenterNew York, New York  10021