Clinical trial NCT00245102: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-10-27
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Overall Response Rate Measured by Complete Response (CR) Rate and Partial Response (PR) Rate as Determined by RECIST
timeFrame: Up to 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Robert Maki
role: PRINCIPAL_INVESTIGATOR
References: