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Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)

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ClinicalTrials.gov Identifier: NCT00330421
Recruitment Status : Completed
First Posted : May 26, 2006
Results First Posted : March 17, 2014
Last Update Posted : April 30, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 25, 2006
First Posted Date  ICMJE May 26, 2006
Results First Submitted Date  ICMJE November 5, 2013
Results First Posted Date  ICMJE March 17, 2014
Last Update Posted Date April 30, 2014
Study Start Date  ICMJE June 2006
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
  • Change in Fludeoxyglucose (FDG) Uptake (Maximal Standardized Uptake Value, or SUVmax) [ Time Frame: Baseline to up to 1 month post-treatment ]
    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
  • Change in Interstitial Fluid Pressure (IFP) [ Time Frame: Baseline to up to 1 month post-treatment ]
    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
  • Change in White Blood Cell Count (WBC) [ Time Frame: Baseline to up to 1 month post-treatment ]
    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
  • Change in Pericyte Coverage of Endothelial Cells (Alpha-SMA) [ Time Frame: Baseline to up to 1 month post-treatment ]
    Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
  • Clinical Benefit as Measured by 50% Reduction in IFP [ Time Frame: Baseline to surgery ]
  • Clinical Benefit, Measured by Any Reduction in Tumor Dimensions on CT Scan as Measured by RECIST Criteria [ Time Frame: Up to 1 month ]
  • Incidence of Adverse Events [ Time Frame: Up to 1 month ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)
Official Title  ICMJE A Phase II Clinical and Correlative Study of BAY 43-9006 (Sorafenib) IND 69,896 in Sarcoma
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
Detailed Description

PRIMARY OBJECTIVES:

I. To determine if the combined vascular endothelial growth factor receptor 2 (VEGF-R2)/platelet-derived growth factor receptor (PDGFR)-beta inhibitor BAY 43-9006/ sorafenib can decrease interstitial fluid pressure (IFP) in soft tissue sarcomas.

II. To investigate the effects of BAY 43-9006/sorafenib on tumor blood flow, circulating endothelial cells, vascular density and pericyte coverage.

III. To characterize the pharmacokinetics of BAY 43-9006/sorafenib in sarcoma patients.

SECONDARY OBJECTIVES:

I. To describe any preliminary evidence of anti-tumor activity. II. Assess whether there are any significant relationships between systemic drug exposure and drug-related toxicity or biological effect.

OUTLINE: This is a multicenter study. Patients are assigned to one of two groups (group 1 closed to accrual as of 5/30/07).

GROUP I (SARCOMAS OF THE EXTREMITY) (CLOSED TO ACCRUAL AS OF 5/30/07): 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.

GROUP II (METASTATIC OR INOPERABLE SARCOMAS): 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.

In both groups, blood samples are drawn periodically for pharmacological studies.

After completion of study therapy, patients are followed monthly until all study-related toxicities are resolved and then at the discretion of the investigator.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Metastatic Osteosarcoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Osteosarcoma
  • Stage I Adult Soft Tissue Sarcoma
  • Stage II Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
Intervention  ICMJE
  • Drug: sorafenib tosylate
    Given PO
    Other Names:
    • BAY 43-9006
    • BAY 43-9006 Tosylate Salt
    • BAY 54-9085
    • Nexavar
    • SFN
  • Procedure: therapeutic conventional surgery
    Undergo surgery
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Procedure: computed tomography
    Correlative studies
    Other Name: tomography, computed
  • Procedure: dynamic contrast-enhanced magnetic resonance imaging
    Correlative studies
    Other Name: DCE-MRI
Study Arms  ICMJE
  • Experimental: Group I (sarcomas of extremity, closed accrual as of 5/30/07)
    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.
    Interventions:
    • Drug: sorafenib tosylate
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
    • Procedure: computed tomography
    • Procedure: dynamic contrast-enhanced magnetic resonance imaging
  • Experimental: Group II (metastatic or inoperable sarcomas)
    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.
    Interventions:
    • Drug: sorafenib tosylate
    • Other: laboratory biomarker analysis
    • Other: pharmacological study
    • Procedure: computed tomography
    • Procedure: dynamic contrast-enhanced magnetic resonance imaging
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 17, 2014)
15
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2008
Actual Primary Completion Date December 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential (age < 50, last menstrual period [LMP] < 12 months ago) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of beta-HCG) within 72 hr prior to receiving the study medication; BAY43-9006 has antiproliferative effects, which may be harmful to the developing fetus or nursing infant
  • Fertile males and females must use adequate contraception
  • Signed informed consent

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00330421
Other Study ID Numbers  ICMJE NCI-2012-03122
05-033
U01CA062490 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeffrey Morgan Dana-Farber Cancer Institute
PRS Account National Cancer Institute (NCI)
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP