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CompletedNCT02050919Updated Mar 21, 2022Results posted

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

A Phase 2 interventional study of Epirubicin Hydrochloride and External Beam Radiation Therapy in Pleomorphic Rhabdomyosarcoma, Stage IIB Adult Soft Tissue Sarcoma AJCC v7 and Stage III Adult Soft Tissue Sarcoma AJCC v7, sponsored by OHSU Knight Cancer Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-21.

Sponsored by OHSU Knight Cancer Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

In context

Sarcoma

1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.

This study's enrollment of 20 is below the median of 40 across 1,283 interventional studies indexed under Sarcoma.

Browse Sarcoma studies →

Lead sponsor

OHSU Knight Cancer Institute is the lead sponsor of 242 studies on the registry; 45 are open to participants now.

Of its 27 completed or terminated interventional studies of FDA-regulated products, 15 (56%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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/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 thirty days after the last administration of sorafenib
  • Women of childbearing potential must have negative serum pregnancy test performed within 7-days prior to registration
  • 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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

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

Interventions

  • DrugEpirubicin Hydrochloride

    Given IV

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

  • RadiationExternal Beam Radiation Therapy

    Undergo EBRT

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

  • DrugIfosfamide

    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

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugSorafenib Tosylate

    Given PO

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

  • ProcedureTherapeutic Conventional Surgery

    Undergo surgical resection

06

What researchers measure

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.

    Time frame: Assessed at surgical resection

Secondary outcomes

  1. Number of Grade 3-4 Adverse Events

    Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

    Time frame: Up to 5 years

  2. Number of Participants With Wound Complications

    Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer.

    Time frame: At least 120 days

  3. Overall Survival at 2 Years

    Percentage of patients alive at 2 years, Method of Kaplan-Meier used.

    Time frame: Time from registration until death from any cause

  4. Overall Disease-free Survival (Stage IIB-III Patients)

    Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier \\used.

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

  5. Distant Disease-free Survival (Stage IIB-III Patients)

    Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used.

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

  6. Number of Participants With Local Recurrence

    Number of patients with local recurrence after surgical resection of the primary tumor

    Time frame: Time from surgical resection until primary analysis ( Median follow-up for local recurrence 17.11 months, range 6.18 - 42.8 months)

07

Results

Posted Jun 11, 2020

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Started20
Completed20
Not completed0

Outcome measures

PrimaryPathologic 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.

Time frame:
Assessed at surgical resection
Reported as:
Number · % of participants
Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.
% of participantsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.20 (5.7 to 43.7)
SecondaryNumber of Grade 3-4 Adverse Events

Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

Time frame:
Up to 5 years
Reported as:
Number · Grade 3-4 Adverse Events
Number of Grade 3-4 Adverse Events
Grade 3-4 Adverse EventsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Number of Grade 3-4 Adverse Events86
SecondaryNumber of Participants With Wound Complications

Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer.

Time frame:
At least 120 days
Reported as:
Count of participants · Participants
Number of Participants With Wound Complications
ParticipantsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Number of Participants With Wound Complications10
SecondaryOverall Survival at 2 Years

Percentage of patients alive at 2 years, Method of Kaplan-Meier used.

Time frame:
Time from registration until death from any cause
Reported as:
Number · percentage of patients
Overall Survival at 2 Years
percentage of patientsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Overall Survival at 2 Years82 (54 to 94)
SecondaryOverall Disease-free Survival (Stage IIB-III Patients)

Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier \\used.

Time frame:
Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 2 years
Reported as:
Median · Months
Overall Disease-free Survival (Stage IIB-III Patients)
MonthsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Overall Disease-free Survival (Stage IIB-III Patients)13.3 (6 to NA)
SecondaryDistant Disease-free Survival (Stage IIB-III Patients)

Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used.

Time frame:
Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 2 years
Reported as:
Median · Months
Distant Disease-free Survival (Stage IIB-III Patients)
MonthsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Distant Disease-free Survival (Stage IIB-III Patients)16.4 (8.9 to NA)
SecondaryNumber of Participants With Local Recurrence

Number of patients with local recurrence after surgical resection of the primary tumor

Time frame:
Time from surgical resection until primary analysis ( Median follow-up for local recurrence 17.11 months, range 6.18 - 42.8 months)
Reported as:
Count of participants · Participants
Number of Participants With Local Recurrence
ParticipantsTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Number of Participants With Local Recurrence0

Adverse events

Collected over Toxicity measure through follow up, every 4 months until patient death or withdrawal, a median of 34.5 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Sorafenib, Chemotherapy, Radiation, Surgery)5/20 (25%)18/20 (90%)20/20 (100%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Febrile NeutropeniaBlood and lymphatic system disorders12/20
wound infectionInfections and infestations7/20
EncephalopathyNervous system disorders3/20
SepsisInfections and infestations3/20
Platelet Count DecreasedInvestigations2/20
Catheter Related infectionInfections and infestations1/20
ConstipationGastrointestinal disorders1/20
DeliriumPsychiatric disorders1/20
DiarrheaGastrointestinal disorders1/20
enterocolitis infectiousInfections and infestations1/20
Most frequent other events
Showing 10 of 97
Most frequent other events
EventTreatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Lymphocyte count decreasedInvestigations20/20
Platelet count decreasedInvestigations20/20
AnemiaBlood and lymphatic system disorders19/20
Neutrophil Count DecreasedInvestigations18/20
White Blood Cell DecreasedInvestigations18/20
HypoalbuminemiaMetabolism and nutrition disorders16/20
HypophosphatemiaMetabolism and nutrition disorders16/20
nauseaGastrointestinal disorders13/20
hypocalcemiaMetabolism and nutrition disorders12/20
HypomagnesemiaMetabolism and nutrition disorders12/20

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Sorafenib, Chemotherapy, Radiation, Surgery)
<=18 years0
Between 18 and 65 years17
>=65 years3
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Female11
Male9
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (Sorafenib, Chemotherapy, Radiation, Surgery)
Hispanic or Latino1
Not Hispanic or Latino18
Unknown or Not Reported1
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Sorafenib, Chemotherapy, Radiation, Surgery)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander1
Black or African American0
White18
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Treatment (Sorafenib, Chemotherapy, Radiation, Surgery)
United States20
08

Study locations

1 site
  • OHSU Knight Cancer Institute
    Portland, Oregon 97239, United States
09

References and documents

Publications

  • 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. PubMed 32827353 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 15, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 21, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02050919
Lead sponsor
OHSU Knight Cancer Institute
Collaborators
Bayer, Oregon Health and Science University
Responsible party
Christopher Ryan (Principal Investigator, OHSU Knight Cancer Institute) — Principal investigator
First posted
Jan 31, 2014
Start date
Dec 3, 2013
Primary completion
May 7, 2018
Completion
Dec 31, 2020
Results posted
Jun 11, 2020
Last update
Mar 21, 2022

Study contacts

Christopher Ryan
principal investigator · OHSU Knight Cancer Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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