Sorafenib and Ifosfamide in Treating Patients With High-Grade Soft Tissue Sarcoma or Bone Sarcoma That Can Be Removed by Surgery

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00880542
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1

Study Details

Study Description

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 ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with ifosfamide may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving sorafenib together with ifosfamide and to see how well it works in treating patients with high-grade soft tissue sarcoma or bone sarcoma that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: sorafenib; Drug: Ifosfamide	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Assess the safety, toxicity, and efficacy of neoadjuvant sorafenib tosylate and ifosfamide in patients with resectable high-grade soft tissue or bone sarcoma.

Secondary

• Assess the long-term efficacy or impact of therapy in these patients, in terms of the duration of local recurrence-free survival, distant recurrence-free survival, and disease-specific survival.

OUTLINE:

• Neoadjuvant therapy: Patients receive oral sorafenib tosylate twice daily on days 1-14 in course 1. Patients then receive oral sorafenib tosylate twice daily on days 1-28 and ifosfamide IV continuously on days 1-7 in courses 2 and 3. Treatment repeats every 14-28 days* for 3 courses.

NOTE: *Course 1 is 14 days in duration; courses 2 and 3 are 28 days in duration.

• Surgery: At least 1 week after the completion of neoadjuvant therapy, patients undergo surgery.

• Adjuvant therapy: Beginning ≥ 3 weeks after surgery, patients who respond to neoadjuvant therapy receive oral sorafenib twice daily for 6 months. Patients also receive 2 courses of ifosfamide as in courses 2 and 3 of neoadjuvant therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sorafenib and Ifosfamide as a Treatment for Patients With Sarcoma
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Nov 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Sorafenib + Ifosfamide * Neoadjuvant therapy: Patients receive oral sorafenib tosylate twice daily on days 1-14 in course 1. Patients then receive oral sorafenib tosylate twice daily on days 1-28 and ifosfamide IV continuously on days 1-7 in courses 2 and 3. Treatment repeats every 14-28 days* for 3 courses. NOTE: *Course 1 is 14 days in duration; courses 2 and 3 are 28 days in duration. Surgery: At least 1 week after the completion of neoadjuvant therapy, patients undergo surgery. Adjuvant therapy: Beginning ≥ 3 weeks after surgery, patients who respond to neoadjuvant therapy receive oral sorafenib twice daily for 6 months. Patients also receive 2 courses of ifosfamide as in courses 2 and 3 of neoadjuvant therapy.

Drug: sorafenib; Patients with sarcoma who have resectable disease will be treated with neoadjuvant sorafenib and ifosfamide. PET/CT will be used to assess the metabolic and radiographic response to therapy.; Drug: Ifosfamide; Patients with sarcoma who have resectable disease will be treated with neoadjuvant ifosfamide and sorafenib. PET/CT will be used to assess the metabolic and radiographic response to therapy.

Outcome Measures

Primary Outcome Measures

1. Using PET/CT Scan to Measure Safety, Toxicity, and Efficacy of Neoadjuvant Sorafenib Tosylate and Ifosfamide in Patients With Resectable High-grade Soft Tissue or Bone Sarcoma. [Participants were followed for duration of study, an average of 1 year.]

   After cycle 1, a limited PET/CT scan of the affected site will be performed to assess response to sorafenib treatment alone. After cycle 3, prior to surgery, a limited PET/CT scan of the affected site will be performed to assess response to the combination sorafenib and ifosfamide treatment.

Secondary Outcome Measures

1. Local and Distant Recurrence-free Survival [conclusion of study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically confirmed high grade sarcoma of the soft tissue or bone

• participants Identified as a proper candidate for ifosfamide-based neoadjuvant therapy

• candidates must have operable disease for which a resection is planned

• ECOG performance status 0-1

• Hemoglobin ≥ 9.0 g/dL

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)

• INR < 1.5 or PT/PTT normal.Concurrent anticoagulation therapy with warfarin or heparin allowed

• Creatinine ≤ 1.5 times ULN

• women of childbearing potential must have negative pregnancy test performed within 7 days prior to start of treatment.

• Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study therapy.

• A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

• known HIV infection

• chronic hepatitis B or C infection

• clinically active serious infection > CTCAE grade 2

• NYHA class III or IV congestive heart failure

• unstable angina (i.e., anginal symptoms at rest) or new onset angina within the past 3 months

• myocardial infarction within the past 6 months

• cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 90 mm Hg) despite optimal medical management

• thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months

• pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks

• other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks

• Any condition that would impair the ability to swallow whole pills

• malabsorption problem

• Any known severe hypersensitivity to sorafenib tosylate or any of its excipients

• known or suspected allergy to sorafenib tosylate or any agent given in this study

• serious nonhealing wound, ulcer, or bone fracture

• evidence or history of bleeding diathesis or coagulopathy

• significant traumatic injury within the past 4 weeks

• major surgery or open biopsy within 4 weeks of starting treatment

• Concomitant St. John's wort or rifampin

• KNown brain metastases. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastases.

• any condition that impairs patients' ability to swallow pills

• any malabsorption problem

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center

Investigators

• Principal Investigator: William Tap, MD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00880542
• Other Study ID Numbers: CDR0000633030; UCLA-0704086; BAYER-UCLA-0704086; ONYX-UCLA-0704086
• First Posted: Apr 13, 2009
• Last Update Posted: Aug 10, 2020
• Last Verified: Jul 1, 2012

• Keywords provided by Jonsson Comprehensive Cancer Center: localized osteosarcoma; stage II adult soft tissue sarcoma; stage III adult soft tissue sarcoma
• Additional relevant MeSH terms: Sarcoma; Sorafenib; Ifosfamide

Study Results

Participant Flow

Recruitment Details	Dates of recruitment period: 08/20/2008 - 07/19/2010 Types of location: Academic medical clinics
Pre-assignment Detail	There are no pre-assignment details to describe

Arm/Group Title	Sorafenib + Ifosfamide
Arm/Group Description
Period Title: Treatment Period (Sorafenib+Ifosfamide)
STARTED	7
COMPLETED	4
NOT COMPLETED	3
Period Title: Treatment Period (Sorafenib+Ifosfamide)
STARTED	4
COMPLETED	4
NOT COMPLETED	0
Period Title: Treatment Period (Sorafenib+Ifosfamide)
STARTED	4
COMPLETED	3
NOT COMPLETED	1
Period Title: Treatment Period (Sorafenib+Ifosfamide)
STARTED	3
COMPLETED	3
NOT COMPLETED	0
Period Title: Treatment Period (Sorafenib+Ifosfamide)
STARTED	0
COMPLETED	0
NOT COMPLETED	0
Period Title: Treatment Period (Sorafenib+Ifosfamide)
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sorafenib + Ifosfamide
Arm/Group Description
Overall Participants	7
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	2 28.6%
Male	5 71.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Using PET/CT Scan to Measure Safety, Toxicity, and Efficacy of Neoadjuvant Sorafenib Tosylate and Ifosfamide in Patients With Resectable High-grade Soft Tissue or Bone Sarcoma.
Description	After cycle 1, a limited PET/CT scan of the affected site will be performed to assess response to sorafenib treatment alone. After cycle 3, prior to surgery, a limited PET/CT scan of the affected site will be performed to assess response to the combination sorafenib and ifosfamide treatment.
Time Frame	Participants were followed for duration of study, an average of 1 year.

Outcome Measure Data

Analysis Population Description

Due to the study closing early and the few number of participants enrolled, the outcome measures were not done.

Arm/Group Title	Sorafenib + Ifosfamide
Arm/Group Description
Measure Participants	0

2. Secondary Outcome

Title	Local and Distant Recurrence-free Survival
Time Frame	conclusion of study

Outcome Measure Data

Analysis Population Description

Due to study closing early and the few number of participants enrolled, the outcome measures were not done.

Arm/Group Title	Sorafenib + Ifosfamide
Arm/Group Description
Measure Participants	0

Adverse Events

Time Frame	Adverse event(AE)data collected between 08/20/2008 and 7/19/2010, therefore AE reporting period is approximately 1 year and 11 months.
Adverse Event Reporting Description	Systemic adverse event assessment with every physician contact day, either as outpatient or inpatient throughout the active treatment phase of the study and every three months in the follow-up period.
Arm/Group Title	Sorafenib + Ifosfamide
Arm/Group Description
All Cause Mortality
	Sorafenib + Ifosfamide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sorafenib + Ifosfamide
	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)
Blood and lymphatic system disorders
Grade 3 and 4 Neutropenic fever related to Ifosfamide	2/7 (28.6%)
Grade 3 thrombocytopenia related to Ifosfamide	1/7 (14.3%)
Grade 3 lymphopenia related to Ifosfamide	1/7 (14.3%)
Grade 4 leukocytopenia related to Ifosfamide	1/7 (14.3%)
Grade 4 Neutopenia related to Ifosfamide	1/7 (14.3%)
Gastrointestinal disorders
Grade 4 bowel perforation due to disease progression	1/7 (14.3%)
Metabolism and nutrition disorders
Grade 3 hypocalcemia related to possible vitamin D insufficiency	1/7 (14.3%)
Musculoskeletal and connective tissue disorders
Grade 3 lower back pain due to disease or GCSF	1/7 (14.3%)
Other (Not Including Serious) Adverse Events
	Sorafenib + Ifosfamide
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Blood and lymphatic system disorders
Anemia	3/7 (42.9%)
Leukocytosis	1/7 (14.3%)
Pancytopenia	1/7 (14.3%)
pedal edema	1/7 (14.3%)
lower extremity edema	1/7 (14.3%)
Cardiac disorders
Tachycardia	2/7 (28.6%)
Chest pain	1/7 (14.3%)
Gastrointestinal disorders
abdominal pain	2/7 (28.6%)
abdominal bloating	1/7 (14.3%)
Anorexia	1/7 (14.3%)
constipation	5/7 (71.4%)
Diarrhea	1/7 (14.3%)
emesis	1/7 (14.3%)
hematemesis	1/7 (14.3%)
hemarrhoids	1/7 (14.3%)
nausea	6/7 (85.7%)
vomiting	2/7 (28.6%)
General disorders
Epistaxis	1/7 (14.3%)
chills	1/7 (14.3%)
Fatigue	2/7 (28.6%)
shaking spells	1/7 (14.3%)
weight loss	1/7 (14.3%)
fever	2/7 (28.6%)
asthenia	1/7 (14.3%)
malnourished	1/7 (14.3%)
pain-incision	1/7 (14.3%)
pain-both feet	1/7 (14.3%)
pain-post surgery	1/7 (14.3%)
throat sore	1/7 (14.3%)
Hepatobiliary disorders
Elevated international normalized ratio (INR)	1/7 (14.3%)
Infections and infestations
Neutropenia fever	1/7 (14.3%)
mouth thrush	1/7 (14.3%)
positive VRE/Enterococolis	1/7 (14.3%)
Metabolism and nutrition disorders
elevated triglyceride	1/7 (14.3%)
hyperglycemia	1/7 (14.3%)
hypokalemia	2/7 (28.6%)
hyponatremia	2/7 (28.6%)
Musculoskeletal and connective tissue disorders
myalgia	1/7 (14.3%)
right glenoid fossa fracture	1/7 (14.3%)
shoulder pain	1/7 (14.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
tumor pain	1/7 (14.3%)
Nervous system disorders
bilateral lower extremities edema	1/7 (14.3%)
dizziness	1/7 (14.3%)
headache	1/7 (14.3%)
pain/tingling left arm	1/7 (14.3%)
somnolence	1/7 (14.3%)
tingling in feet	1/7 (14.3%)
Psychiatric disorders
altered mental status	1/7 (14.3%)
confusion	1/7 (14.3%)
difficulty concentrating	1/7 (14.3%)
insomnia	2/7 (28.6%)
Renal and urinary disorders
dysuria	1/7 (14.3%)
urine incontinence	1/7 (14.3%)
urine pH less than 8	1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
hemoptysis	1/7 (14.3%)
hiccups	1/7 (14.3%)
productive cough	1/7 (14.3%)
cough	4/7 (57.1%)
wheezing	1/7 (14.3%)
Skin and subcutaneous tissue disorders
alopecia	2/7 (28.6%)
anal fissure	1/7 (14.3%)
bleeding with bowel movement	1/7 (14.3%)
calluses, finger/toes	1/7 (14.3%)
desquamation	1/7 (14.3%)
ecchymosis below left eye	1/7 (14.3%)
hand-foot syndrome	1/7 (14.3%)
Lt. heel plantar foot tenderness	1/7 (14.3%)
Painful blister on hand	1/7 (14.3%)
Pionidal hidratitis	1/7 (14.3%)
Pruritus	2/7 (28.6%)
Purpura right arm	1/7 (14.3%)
Rash, hands/feet	1/7 (14.3%)
redness areas under bunions	1/7 (14.3%)
Vascular disorders
volume depletion	1/7 (14.3%)
deep vein thrombosis, right upper extremity	1/7 (14.3%)
Hypertension	2/7 (28.6%)

Limitations/Caveats

This study lost funding and was not able to enroll enough participants to do a complete review.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.