Trial record 17 of 346 for:    Open Studies | "Sarcoma"

Sorafenib Tosylate, Combination Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With High-Risk Stage IIB-IV Soft Tissue Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by OHSU Knight Cancer Institute
Sponsor:
Collaborators:
Bayer
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT02050919
First received: January 29, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

This phase II trial studies how well sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery work in treating patients with high-risk stage IIB-IV soft tissue sarcoma. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin hydrochloride 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 sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery may be an effective treatment for soft tissue sarcoma.


Condition Intervention Phase
Stage IIB Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Drug: sorafenib tosylate
Drug: epirubicin hydrochloride
Drug: ifosfamide
Radiation: external beam radiation therapy
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib With Chemotherapy, Radiation, and Surgery for High-Risk Soft Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Pathologic response rate, classified as either greater than or equal to 95% necrosis or less than 95% necrosis [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized.


Secondary Outcome Measures:
  • Levels of toxicity, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Wound complication rate [ Time Frame: At least 120 days ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Time from registration until death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Method of Kaplan-Meier will be used.

  • Overall disease-free survival (stage IIB-III patients) [ Time Frame: Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Method of Kaplan-Meier will be used.

  • Distant disease-free survival (stage IIB-III patients) [ Time Frame: Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Method of Kaplan-Meier will be used.

  • Local disease-free survival [ Time Frame: Time from surgical resection of the primary tumor until local recurrence or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Method of Kaplan-Meier will be used.


Estimated Enrollment: 20
Study Start Date: December 2013
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sorafenib, chemotherapy, radiation, surgery)
Patients receive sorafenib tosylate PO QD on days 1-71 and 85-155, epirubicin hydrochloride IV over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo EBRT on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98.
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: epirubicin hydrochloride
Given IV
Other Names:
  • 4'-epi-doxorubicin HCl
  • 4'-epiadriamycin
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Radiation: external beam radiation therapy
Undergo EBRT
Other Name: EBRT
Procedure: therapeutic conventional surgery
Undergo surgical resection
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the pathologic response rate (>= 95% necrosis) after preoperative treatment with sorafenib (sorafenib tosylate), epirubicin (epirubicin hydrochloride), ifosfamide, and hypofractionated radiation for high risk soft tissue sarcomas of the extremities or body wall.

SECONDARY OBJECTIVES:

I. To further characterize the safety of sorafenib plus chemoradiotherapy, including wound complication rate.

II. To estimate time-to-event rates, including overall survival, overall disease-free survival, distant disease-free survival, and local disease-free survival in patients with high risk soft tissue sarcomas of the extremities or body wall treated with preoperative sorafenib plus chemoradiotherapy and postoperative sorafenib plus chemotherapy.

OUTLINE:

Patients receive sorafenib tosylate orally (PO) once daily (QD) on days 1-71 and 85-155, epirubicin hydrochloride intravenously (IV) over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo external beam radiation therapy (EBRT) on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98.

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed, soft-tissue sarcoma: excluding rhabdomyosarcoma (pleomorphic rhabdomyosarcoma patients are eligible), Ewing's, primitive neuroectodermal tumor (PNET), osteosarcoma, or gastrointestinal stromal tumor
  • American Joint Committee on Cancer (AJCC) (7th edition) stage IIb, III, or IV patients planned for resection of the primary tumor

    • > 5 cm in greatest dimension
    • Intermediate or high-grade
    • Superficial or deep
  • Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on body wall
  • Intermediate or high-grade: grades 2 or 3 on scale of 1-3
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Absolute neutrophil count (ANC) >= 1500/cubic milliliter (uL)
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • Platelets >= 100,000/uL
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x ULN
  • International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits; patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate; for patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable
  • No prior chemotherapy, radiation, or biotherapy
  • No major surgery within 4 weeks prior to study entry
  • No contraindications to limb-sparing surgery; patient should be evaluated by a surgeon who specializes in sarcoma resections prior to study enrollment to ensure patient (pt) is a candidate for limb-sparing surgery
  • No severe peripheral vascular disease
  • Adequate contraception must be used and patients must not be pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; men and women should use adequate birth control for at least three months after the last administration of sorafenib
  • Women of childbearing potential must have negative serum pregnancy test performed within 7-days prior to the start of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Patient must sign a study-specific consent form prior to registration
  • Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

  • Patients with known brain metastases; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastases
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2, symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular arrhythmia requiring anti-arrhythmic therapy, or psychiatric illness/social situations that would limit compliance with study requirements; patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
  • Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery or significant traumatic injury within 4 weeks of first study drug
  • Use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  • Pregnant or lactating women are excluded from this study
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse
  • Any uncontrolled thyroid disease
  • Requirement for hemodialysis or peritoneal dialysis
  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: NCT02050919

Locations
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Christopher W. Ryan    503-494-1080    holtorfm@ohsu.edu   
Principal Investigator: Christopher W. Ryan         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Bayer
Investigators
Principal Investigator: Christopher Ryan OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02050919     History of Changes
Other Study ID Numbers: 9464, NCI-2013-02414, 9464, P30CA069533
Study First Received: January 29, 2014
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Epirubicin
Isophosphamide mustard
Sorafenib
Ifosfamide
Niacinamide
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Protein Kinase Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014