Skip to main content
Clinical Trials/NCT00822848
NCT00822848CompletedPhase 1

Antiangiogenic Potentiation of Preoperative Chemoradiotherapy for High Risk Extremity Soft Tissue Sarcomas: A Phase I Study of Sorafenib With Epirubicin, Ifosfamide, Hypofractionated Radiation, and Surgery

OHSU Knight Cancer Institute1 site in 1 country18 target enrollmentStarted: February 2009Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 1
Status
Completed
Enrollment
18
Locations
1
Primary Endpoint
Maximum tolerated dose (MTD) of sorafenib tosylate when combined with chemoradiotherapy

Study Overview

Brief Summary

RATIONALE: 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. Drugs used in chemotherapy, such as epirubicin and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with epirubicin, ifosfamide, and radiation therapy followed by surgery in treating patients with high-risk stage II or stage III soft tissue sarcoma.

Detailed Description

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of sorafenib tosylate when combined with epirubicin hydrochloride, ifosfamide, and hypofractionated radiotherapy prior to surgery in patients with high-risk stage II or III soft tissue sarcoma of the extremity or body wall.

Secondary

  • To examine, preliminarily, the activity of this regimen, in terms of time to local recurrence, distant disease-free survival, progression-free survival, overall survival, and histologic necrosis rate of ≥ 95%, in these patients.
  • To investigate levels of tumorigenic and angiogenic markers, including phosphorylated extracellular signal-regulated kinase (p-ERK), vascular endothelial growth factor (VEGF), serum vascular endothelial growth factor receptor-2 (sVEGFR-2), and basic fibroblast growth factor (bFGF), in plasma and tumor tissue samples at baseline and during and after treatment.
  • To evaluate expression of tumor proliferation and angiogenic factors, including p-ERK, vascular endothelial growth factor receptor-2 (VEGFR2) and Platelet-derived growth factor receptor (PDGFR), in tumor tissue samples as measured by Immunohistochemistry (IHC).

Study Design

Study Type
Interventional
Allocation
Na
Intervention Model
Single Group
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
15 Years to 120 Years (Child, Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Arms & Interventions

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: epirubicin hydrochloride (Drug)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: ifosfamide (Drug)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: laboratory biomarker analysis (Other)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: sorafenib tosylate (Drug)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: immunoenzyme technique (Other)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: immunohistochemistry staining method (Other)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: adjuvant therapy (Procedure)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: neoadjuvant therapy (Procedure)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: therapeutic conventional surgery (Procedure)

Sorafenib, Epirubicin, Ifosfamide

Experimental

Intervention: hypofractionated radiation therapy (Radiation)

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD) of sorafenib tosylate when combined with chemoradiotherapy

Time Frame: The first 8 weeks of therapy, but dose limiting toxicity (DLTs) will be monitored throughout the entire 22 week treatment

The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of patients. Dose level escalation will be determined based on DLTs observed through the first 8 weeks of therapy, but DLTs will be monitored throughout the entire 22 week treatment course and dose de-escalation may occur if excess late DLTs are observed.

Safety

Time Frame: As necessary and at the discretion of the principal investigator

As necessary and at the discretion of the principal investigator, a given dose level may be expanded by 3-6 subjects to further explore the safety of that dose level upon prior written approval of the Institutional Review Board (IRB).

Secondary Outcomes

  • Distant disease-free survival(Registration until development of distant metastatic disease or death, whichever occurs first.)
  • Time to local recurrence(From surgical resection of the primary tumor until local recurrence)
  • Histologic necrosis rate of ≥ 95%(Examined for pathologic response at the time of surgery.)
  • Expression of tumor proliferation and angiogenic factors, including p-ERK, VEGFR2 and PDGFR, in tumor tissue samples as measured by IHC(baseline, week 2 (after sorafenib run-in), and then every 3 weeks through completion of treatment.)
  • Progression-free survival(Registration to progressive disease (per RECIST))
  • Overall survival(Registration until death from any cause.)
  • Levels of tumorigenic and angiogenic markers, including p-ERK, VEGF, sVEGFR-2, bFGF, in plasma and tumor tissue samples as measured by ELISA(Baseline, during, and after treatment with sorafenib plus chemoradiotherapy)

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Christopher Ryan

Principal Investigator

OHSU Knight Cancer Institute

Study Sites (1)

Loading locations...

Similar Trials