Radiation Therapy, Sorafenib, and Surgery in Treating Patients With Soft Tissue Sarcoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert J. Canter, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00805727
First received: December 9, 2008
Last updated: May 20, 2014
Last verified: May 2014

December 9, 2008
May 20, 2014
May 2009
December 2012   (final data collection date for primary outcome measure)
  • Maximal-tolerated dose of sorafenib tosylate when combined with conformal radiotherapy (Phase I) [ Time Frame: Dec 2012 ] [ Designated as safety issue: Yes ]
  • Pathological tumor response by RECIST criteria (Phase II) [ Time Frame: Dec 2012 ] [ Designated as safety issue: No ]
  • Maximal-tolerated dose of sorafenib tosylate when combined with conformal radiotherapy (Phase I)
  • Pathological tumor response by RECIST criteria (Phase II)
Complete list of historical versions of study NCT00805727 on ClinicalTrials.gov Archive Site
  • Toxicities [ Time Frame: Dec 2012 ] [ Designated as safety issue: Yes ]
  • Radiographic response rate by RECIST criteria [ Time Frame: Dec 2012 ] [ Designated as safety issue: No ]
  • Time to local recurrence, local disease-free survival (DFS), distant DFS, overall DFS, progression-free survival, and overall survival [ Time Frame: Dec 2012 ] [ Designated as safety issue: No ]
  • Transfer constant and the initial area under the gadolinium concentration time curve (phase II) [ Time Frame: Dec 2012 ] [ Designated as safety issue: No ]
  • Toxicities
  • Rate of R0, R1, and R2
  • Radiographic response rate by RECIST criteria
  • Time to local recurrence, local disease-free survival (DFS), distant DFS, overall DFS, progression-free survival, and overall survival
  • Transfer constant and the initial area under the gadolinium concentration time curve (phase II)
Not Provided
Not Provided
 
Radiation Therapy, Sorafenib, and Surgery in Treating Patients With Soft Tissue Sarcoma
Phase I/II Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients With Soft Tissue Sarcoma of the Extremity and Body Wall

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving sorafenib together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of radiation therapy given together with sorafenib followed by surgery in treating patients with soft tissue sarcoma.

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of sorafenib tosylate when combined with conformal external beam radiotherapy prior to resection with curative intent in patients with soft tissue sarcoma of the extremity or body wall. (Phase I)
  • To determine the rate of near-complete (≥ 95% tumor necrosis) pathological response to this regimen in these patients. (Phase II)

Secondary

  • To describe the toxicities associated with this regimen.
  • To determine the rate of R0 (negative resection margin), R1 (microscopically positive resection margin), and R2 (macroscopically positive resection margin) following this regimen.
  • To determine the radiographic response rate to this regimen as defined by conventional RECIST criteria.
  • To obtain preliminary data regarding local disease control, distant disease control, progression-free survival, and overall survival with this regimen.

OUTLINE: This is a phase I dose-escalation study of sorafenib tosylate followed by a phase II study.

Patients receive oral sorafenib tosylate twice daily on days 1-35 and undergo conformal radiotherapy 5 days a week for 5 weeks.

Patients undergo dynamic contrast-enhanced MRI scanning at baseline and day 63 followed by surgical resection on day 70.

After completion of study therapy, patients are followed every 4 months.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Sarcoma
  • Drug: sorafenib tosylate
  • Procedure: neoadjuvant therapy
  • Procedure: therapeutic conventional surgery
  • Radiation: 3-dimensional conformal radiation therapy
single treatment arm
sorafenib
Interventions:
  • Drug: sorafenib tosylate
  • Procedure: neoadjuvant therapy
  • Procedure: therapeutic conventional surgery
  • Radiation: 3-dimensional conformal radiation therapy
Canter RJ, Borys D, Olusanya A, Li CS, Lee LY, Boutin RD, Christensen SD, Tamurian RM, Monjazeb AM. Phase I trial of neoadjuvant conformal radiotherapy plus sorafenib for patients with locally advanced soft tissue sarcoma of the extremity. Ann Surg Oncol. 2014 May;21(5):1616-23. doi: 10.1245/s10434-014-3543-7. Epub 2014 Feb 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
December 2012
December 2012   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed soft tissue sarcoma located on the extremity or body wall and meeting 1 of the following criteria:

    • Intermediate- or high-grade disease > 5 cm in maximal dimension
    • Low-grade disease > 8 cm in maximal dimension
  • No evidence of regional or distant metastatic disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Hemoglobin ≥ 9.0 g/dL
  • ANC ≥ 1,500/mm^3
  • Platelets ≥ 100,000/mm^3
  • Total bilirubin ≤ 1.5 mg/dL (unless elevated due to Gilbert's syndrome)
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • INR < 1.5 or PT/PTT within normal limits
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception (men must use effective contraception for ≥ 3 months after completion of study treatment)
  • Able to swallow whole pills
  • None of the following cardiac conditions:

    • NYHA class III-IV congestive heart failure
    • Unstable angina (i.e., anginal symptoms at rest)
    • New-onset angina (beginning within the past 3 months)
    • Myocardial infarction within the past 6 months
    • History of cardiac ventricular arrhythmia requiring ongoing anti-arrhythmic therapy
    • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management
  • No prior clinical or laboratory evidence of bleeding diathesis or coagulopathy
  • No thrombotic or embolic events (e.g., cerebrovascular accident including transient ischemic attacks) within the past 6 months
  • No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks
  • No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks
  • No significant traumatic injury in the past 4 weeks
  • No active malabsorption problem not controlled with medical therapy
  • No active clinically serious infection > CTCAE grade 2
  • No known HIV infection or chronic hepatitis B or C
  • No known or suspected allergy to sorafenib tosylate or any agent given in this study
  • No indwelling metal that would preclude patient from undergoing DCE-MRI

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior major surgery
  • No prior or other concurrent preoperative investigational treatment
  • No other concurrent cancer-directed therapy
  • No concurrent St. John's wort or rifampin
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00805727
CDR0000628781, UCDCC-216, BAYER-UCDCC-216
No
Robert J. Canter, MD, University of California, Davis
University of California, Davis
National Cancer Institute (NCI)
Principal Investigator: Robert Canter, MD University of California, Davis
University of California, Davis
May 2014

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