NCT00822848

Sorafenib, Epirubicin, Ifosfamide, and Radiation Therapy Followed By Surgery in Treating Patients With High-Risk Stage II or Stage III Soft Tissue Sarcoma

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 15 Years – 120 Years
• Healthy volunteers: Not accepted

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). OUTLINE: This is a dose-escalation study of sorafenib tosylate. Patients receive oral sorafenib tosylate\* once or twice daily beginning 2 weeks before the initiation of chemotherapy and continuing until the completion of chemotherapy. Patients also receive epirubicin hydrochloride\*\* IV and ifosfamide IV over 90 minutes on days 1-3 and pegfilgrastim subcutaneously (SC) on day 4 or filgrastim (G-CSF) (SC) daily beginning on day 4 and continuing for up to 10 days or until blood counts recover. Chemotherapy repeats approximately every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. During course 2, patients also undergo 8 fractions of external beam radiotherapy once daily between days 1-10 for a total dose of 28 Gy. Between courses 3 and 4, patients undergo surgical resection. Beginning approximately 2 weeks after surgical resection, patients with positive surgical margins undergo 6 fractions of boost external beam radiotherapy once daily for a total dose of 12 Gy. NOTE: \*Sorafenib is discontinued 1 week before surgery and resumed 1 week after surgery. NOTE: \*\*Epirubicin is omitted during course 2. Plasma and tumor tissue samples are collected periodically for correlative laboratory studies. Plasma and tumor tissue samples are analyzed by ELISA for measurement of tumorigenic and angiogenic markers, including p-ERK, VEGF, sVEGFR-2, and bFGF. Tumor tissue samples are also analyzed by IHC for p-ERK, VEGFR2, phospho-VEGFR2, PDGFR, and phospho-PDGFR. After completion of study therapy, patients are followed periodically.

Conditions

• Sarcoma

Interventions

Type	Name	Description
DRUG	epirubicin hydrochloride	I.V., days 1-3 of each cycle. Epirubicin to be omitted during cycle 2 (concomitant chemoradiation)
DRUG	ifosfamide	Over 90 minutes I.V., days 1-3 of each cycle. Administered with hydration and Mesna.
DRUG	sorafenib tosylate	P.O. daily beginning 2 weeks before first chemotherapy cycle, held 1 week before and after surgery.
OTHER	immunoenzyme technique
OTHER	immunohistochemistry staining method
OTHER	laboratory biomarker analysis
PROCEDURE	adjuvant therapy	Preoperative administration has been the preference at our institution.
PROCEDURE	neoadjuvant therapy
PROCEDURE	therapeutic conventional surgery	Surgery should be planned for 2-4 weeks after the initiation of chemotherapy for cycle 3.
RADIATION	hypofractionated radiation therapy	28 Gy (350 centigray (cGy) x 8 fractions in 10 days) beginning at the start of cycle 2. \*Boost: postoperative boost of 12 Gy (200 cGy x 6 fractions) for patients with positive surgical margins only.

Timeline

• Start date: 2009-02-01
• Primary completion: 2012-09-01
• Completion: 2013-04-30
• First posted: 2009-01-15
• Last updated: 2018-09-07

Locations

1 site across 1 country: United States