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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
  Purpose

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.


Condition Intervention Phase
Sarcoma
Drug: sorafenib tosylate
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients With Soft Tissue Sarcoma of the Extremity and Body Wall

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 15
Study Start Date: May 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
single treatment arm
sorafenib
Drug: sorafenib tosylate Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Radiation: 3-dimensional conformal radiation therapy

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805727

Locations
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Robert Canter, MD University of California, Davis
  More Information

Additional Information:
No publications provided by University of California, Davis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert J. Canter, MD, MD, University of California, Davis
ClinicalTrials.gov Identifier: NCT00805727     History of Changes
Other Study ID Numbers: CDR0000628781, UCDCC-216, BAYER-UCDCC-216
Study First Received: December 9, 2008
Last Updated: May 20, 2014
Health Authority: United States: UCDMC Internal Review Board

Keywords provided by University of California, Davis:
stage I adult soft tissue sarcoma
stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014