NCT00330421

Brief Summary

This phase II trial is studying how well sorafenib works in treating patients with soft tissue sarcoma. Sorafenib may stop the growth of soft tissue sarcoma by blocking blood flow to the tumor and blocking some of the enzymes needed for tumor cell growth

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2006

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 25, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 26, 2006

Completed
6 days until next milestone

Study Start

First participant enrolled

June 1, 2006

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2007

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2008

Completed
5.7 years until next milestone

Results Posted

Study results publicly available

March 17, 2014

Completed
Last Updated

April 30, 2014

Status Verified

November 1, 2013

Enrollment Period

1.5 years

First QC Date

May 25, 2006

Results QC Date

November 5, 2013

Last Update Submit

April 1, 2014

Conditions

Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal TumorMetastatic OsteosarcomaRecurrent Adult Soft Tissue SarcomaRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal TumorRecurrent OsteosarcomaStage I Adult Soft Tissue SarcomaStage II Adult Soft Tissue SarcomaStage III Adult Soft Tissue SarcomaStage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (7)

  • Change in Fludeoxyglucose (FDG) Uptake (Maximal Standardized Uptake Value, or SUVmax)

    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.

    Baseline to up to 1 month post-treatment

  • Change in Interstitial Fluid Pressure (IFP)

    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.

    Baseline to up to 1 month post-treatment

  • Change in White Blood Cell Count (WBC)

    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.

    Baseline to up to 1 month post-treatment

  • Change in Pericyte Coverage of Endothelial Cells (Alpha-SMA)

    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.

    Baseline to up to 1 month post-treatment

  • Clinical Benefit as Measured by 50% Reduction in IFP

    Baseline to surgery

  • Clinical Benefit, Measured by Any Reduction in Tumor Dimensions on CT Scan as Measured by RECIST Criteria

    Up to 1 month

  • Incidence of Adverse Events

    Up to 1 month

Study Arms (2)

Group I (sarcomas of extremity, closed accrual as of 5/30/07)

EXPERIMENTAL

Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.

Drug: sorafenib tosylateProcedure: therapeutic conventional surgeryOther: laboratory biomarker analysisOther: pharmacological studyProcedure: computed tomographyProcedure: dynamic contrast-enhanced magnetic resonance imaging

Group II (metastatic or inoperable sarcomas)

EXPERIMENTAL

Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.

Drug: sorafenib tosylateOther: laboratory biomarker analysisOther: pharmacological studyProcedure: computed tomographyProcedure: dynamic contrast-enhanced magnetic resonance imaging

Interventions

sorafenib tosylateDRUG

Given PO

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN
Group I (sarcomas of extremity, closed accrual as of 5/30/07)Group II (metastatic or inoperable sarcomas)
therapeutic conventional surgeryPROCEDURE

Undergo surgery

Group I (sarcomas of extremity, closed accrual as of 5/30/07)
laboratory biomarker analysisOTHER

Correlative studies

Group I (sarcomas of extremity, closed accrual as of 5/30/07)Group II (metastatic or inoperable sarcomas)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Group I (sarcomas of extremity, closed accrual as of 5/30/07)Group II (metastatic or inoperable sarcomas)
computed tomographyPROCEDURE

Correlative studies

Also known as: tomography, computed
Group I (sarcomas of extremity, closed accrual as of 5/30/07)Group II (metastatic or inoperable sarcomas)
dynamic contrast-enhanced magnetic resonance imagingPROCEDURE

Correlative studies

Also known as: DCE-MRI
Group I (sarcomas of extremity, closed accrual as of 5/30/07)Group II (metastatic or inoperable sarcomas)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • There are two groups of patients eligible for this study; treatment group 1 consists of patients with extremity sarcomas other than potentially curable osteosarcoma or Ewing's sarcoma who are candidates for potentially curative surgery; treatment group 2 consists of patients with metastatic or inoperable sarcoma, for which there is no known curative or survival prolonging palliative therapy, or failure of these therapies; patients must have at least one site of measurable disease by radiologic imaging techniques; patients must have at least one palpable tumor mass with no overlying viscera which is amenable to biopsy; the tumor mass should be approximately 2 cm or greater in diameter; patients with smaller palpable tumors are eligible if participation is approved by the treating surgeon after discussion with the study chairperson
  • As of 5/30/07, no subjects will accrue to Treatment Group I
  • Life expectancy \>= 2 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
  • Pretreatment laboratory data, obtained within 14 days of study entry, must meet the following criteria:
  • Absolute Neutrophil Count (ANC) \>= 1,500/mm\^3
  • Platelets \>= 100,000/mm\^3
  • Serum glutamic oxaloacetic transaminase (SGOT) =\< 2.5-times the upper limit of normal (ULN)
  • Serum glutamic-pyruvic transaminase (SGPT)=\< 2.5-times ULN
  • Total Bilirubin =\< ULN
  • Serum creatinine =\< 1.5-times ULN
  • \>= 3 weeks since major surgery unrelated to study disease (sarcoma)
  • \>= 3 weeks since chemotherapy or radiation therapy (6 weeks for nitrosourea or mitomycin C chemotherapy)
  • No prior treatment with sorafenib (BAY 43-9006) or specific inhibitors of mitogen-activated protein kinase (MAPK) pathways are permitted; a previously irradiated tumor site cannot be used for clinical or correlative measurements, although irradiation to sites other than a measurable site is permitted; there are no limitations on the extent or type of prior therapy received by the patient other than the time intervals indicated in the above and demonstrating complete recovery from any adverse effects associated by satisfying all relevant eligibility criteria
  • Patients who are on warfarin anticoagulation are allowed to participate as long as they are converted to a low molecular weight heparin (e.g. lovenox) from study entry until at least day 56
  • +3 more criteria

You may not qualify if:

  • Ewing's sarcoma or osteosarcoma that is potentially curable with surgery, chemotherapy, and/or radiation therapy
  • Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirements for steroids, or enzyme-inducing anti-convulsant agents, or clinical symptoms of/from brain metastases; patients with treated and/or stable brain metastasis who are asymptomatic can be enrolled, if otherwise eligible
  • Any uncontrolled serious medical or psychiatric illness; particular note is given to uncontrolled hypertension (discretion left to investigators) and significant proteinuria \> 1 gm/24 hr (does not require quantitation in absence of clinical indication)
  • Patients receiving other investigational agents
  • Human immunodeficiency virus (HIV) patients receiving combination anti-retroviral therapy are excluded because of potential pharmacokinetic interactions

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

  • Raut CP, Boucher Y, Duda DG, Morgan JA, Quek R, Ancukiewicz M, Lahdenranta J, Eder JP, Demetri GD, Jain RK. Effects of sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with refractory sarcomas (NCI protocol 6948). PLoS One. 2012;7(2):e26331. doi: 10.1371/journal.pone.0026331. Epub 2012 Feb 7.

    PMID: 22347360DERIVED

MeSH Terms

Conditions

Neuroectodermal Tumors, Primitive, PeripheralOsteosarcomaSarcoma

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNeoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Limitations and Caveats

No Grade 4 toxicities were noted (15 patients). IFP measurements were obtained in only 6 of 15 patients at baseline. Only 2 of these 6 patients had SD at 28 and 56 days and therefore, second IFP measurements were only obtained in those 2 patients.

Results Point of Contact

Title
Jeffrey A. Morgan, M.D.
Organization
Dana-Farber Cancer Institute
jamorgan@partners.org
617-632-5204

Study Officials

  • Jeffrey Morgan

    Dana-Farber Cancer Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 25, 2006

First Posted

May 26, 2006

Study Start

June 1, 2006

Primary Completion

December 1, 2007

Study Completion

July 1, 2008

Last Updated

April 30, 2014

Results First Posted

March 17, 2014

Record last verified: 2013-11

Locations

US(1)