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

Official Title: “A Phase II Study of Sorafenib and Ifosfamide as a Treatment for Patients With Sarcoma”

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.

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.

Intervention(s) in this Clinical Trial

• 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.

Arms, Groups and Cohorts in this Clinical Trial

• 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.

Primary Measures

• 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.
  • Time Frame: Participants were followed for duration of study, an average of 1 year.
    Safety Issue?: Yes

Secondary Measures

• Local and Distant Recurrence-free Survival
  • Time Frame: conclusion of study
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of California, Los Angeles Other

Overall Clinical Trial Officials and Contacts

William Tap, MD Principal Investigator Jonsson Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00880542

Study ID Number: CDR0000633030

ClinicalTrials.gov Identifier: NCT00880542

Health Authority: United States: Food and Drug Administration