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

NCT ID: NCT00245102

Last Updated: 2014-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2011-03-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

sorafenib tosylate

Intervention Type: DRUG

Given orally

Interventions

sorafenib tosylate

Given orally

Intervention Type: DRUG

Other Intervention Names

BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Maki

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2012-01469

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-7060

Identifier Type: -

Identifier Source: secondary_id

CDR0000449962

Identifier Type: -

Identifier Source: secondary_id

MSKCC-05081

Identifier Type: -

Identifier Source: secondary_id

05-081

Identifier Type: OTHER

Identifier Source: secondary_id

7060

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01469

Identifier Type: -

Identifier Source: org_study_id