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

NCT02050919 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00009464NCI-2013-02414
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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, by stopping them from dividing, or by stopping them from spreading. 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.

Conditions

Pleomorphic Rhabdomyosarcoma; Stage IIB Adult Soft Tissue Sarcoma AJCC v7; Stage III Adult Soft Tissue Sarcoma AJCC v7; Stage IV Adult Soft Tissue Sarcoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.

  Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized.

  Assessed at surgical resection

Secondary Outcomes (6)

• Number of Grade 3-4 Adverse Events

  Up to 5 years

• Number of Participants With Wound Complications

  At least 120 days

• Overall Survival at 2 Years

  Time from registration until death from any cause

• Overall Disease-free Survival (Stage IIB-III Patients)

  Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 2 years

• Distant Disease-free Survival (Stage IIB-III Patients)

  Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 2 years

Study Arms (1)

Treatment (sorafenib, chemotherapy, radiation, surgery)

EXPERIMENTAL

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: Epirubicin Hydrochloride; Radiation: External Beam Radiation Therapy; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Drug: Sorafenib Tosylate; Procedure: Therapeutic Conventional Surgery

Interventions

Epirubicin Hydrochloride DRUG

Given IV

Also known as: Ellence, IMI-28, Pharmorubicin PFS

Treatment (sorafenib, chemotherapy, radiation, surgery)

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation

Treatment (sorafenib, chemotherapy, radiation, surgery)

Ifosfamide DRUG

Given IV

Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

Treatment (sorafenib, chemotherapy, radiation, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sorafenib, chemotherapy, radiation, surgery)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Treatment (sorafenib, chemotherapy, radiation, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Treatment (sorafenib, chemotherapy, radiation, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Bayer: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

  PMID: 32827353 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Epirubicin; Ifosfamide; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: Christopher Ryan, MD
• Organization: OHSU Knight Cancer Institute

ryanc@ohsu.edu

503-494-8487

Study Officials

• Christopher Ryan

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 29, 2014
• First Posted: January 31, 2014
• Study Start: December 3, 2013
• Primary Completion: May 7, 2018
• Study Completion: December 31, 2020
• Last Updated: March 21, 2022
• Results First Posted: June 11, 2020

Record last verified: 2022-02

Locations

US (1)