Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma

• Status: Completed
• Trial end date: 2013-08-01
• Target enrollment: 0
• Participant gender: Female

Summary

This phase II trial is studying how well ziv-aflibercept works in treating patients with locally advanced, unresectable or metastatic gynecologic soft tissue sarcoma. Ziv-aflibercept 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aflibercept; Endothelial Growth Factors

Criteria

Inclusion Criteria:

• Histologically/cytologically confirmed soft tissue sarcoma of gynecologic tract including 1 of the following subtypes: uterine leiomyosarcoma, malignant mixed mullerian tumor/carcinosarcoma, disease originating in ovary/fallopian tube allowed

• Locally advanced/unresectable/metastatic disease

• Previously treated disease must have radiographic/clinical evidence of PD

• Measurable disease-at least 1 lesion in at least 1 dimension (longest diameter) as >=20mm with conventional techniques or as >=10mm with spiral CT scan

• Indicator lesions may not have been previously treated with surgery/radiotherapy/radiofrequency ablation unless PD has been confirmed

• ECOG PS 0-2 OR Karnofsky PS 60-100%

• Life expectancy>=3 months

• WBC>=3,000/mm^3

• Absolute neutrophil count>=1,500/mm^3

• Platelet count>=75,000/mm^3

• Bilirubin=<1.5xULN

• AST and ALT=<3xULN

• INR=<1.5 (unless on warfarin)

• Creatinine=<1.5xULN OR creatinine clearance>=60 mL/min

• Urine protein<1+ by dipstick OR 24-hour urine protein<500 mg OR urine protein:creatinine ratio<1

• Not pregnant/nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥6 months after treatment - No other active malignancy within past 5 years except adequately treated cervical carcinoma in situ/nonmelanoma skin cancer

• No known hypersensitivity to Chinese hamster ovary cell products/other recombinant human antibodies

• No history of allergic reactions attributed to compounds of similar chemical/biological composition to study agents

• No serious/nonhealing wound/ulcer/bone fracture

• No abdominal fistula/gastrointestinal perforation/bowel obstruction/intraabdominal abscess within past 28 days

• No significant traumatic injuries within past 28 days

• No evidence of bleeding diathesis/coagulopathy

• No uncontrolled intercurrent illness including but not limited to: Ongoing/active infection, psychiatric illness or social situations that would preclude study compliance

• <=2 prior cytotoxic chemotherapy regimen for recurrent, locally advanced or metastatic disease

• Recovered from prior therapy

• No prior antiangiogenic agent

Exclusion Criteria:

• < 4weeks since prior chemotherapy (<6 weeks for nitrosoureas/carmustine/mitomycin C), prior investigational treatment, radiotherapy and major surgery/open biopsy

• 1 week since prior core biopsy

• 1 month since prior thrombolytic agents

• Concurrent full-dose anticoagulants with INR>1.5 allowed if: In-range INR (usually between 2-3) on stable dose of oral anticoagulant or low molecular weight heparin,

• OR; For patients on warfarin, the upper target for INR is ≤3 No active bleeding/pathological condition that carries a high risk of bleeding (e.g. tumor invading major vessels/known varices)

• No evidence of CNS disease including primary brain tumor/brain metastasis

• No other concurrent investigational agents - No concurrent major surgery

• No concurrent combination antiretroviral therapy for HIV-positive patients

• Clinically significant cardiovascular disease including:

• Cerebrovascular accident within past 6 months,

• Uncontrolled hypertension defined as BP>150/100mmHg OR systolic BP>180mmHg if diastolic BP<90 mmHg, on ≥2 repeated determinations on separate days within past 3 months,

• OR; Antihypertensive medications allowed as long as dose and number of antihypertensive medications have not increased within past 2 weeks, Myocardial infarction, coronary artery bypass graft, or unstable angina within past 6 months, OR;

• OR; NYHA class III-IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris within past 6 months, Clinically significant peripheral vascular disease within past 6 months

• OR; pulmonary embolism, deep vein thrombosis, or other thromboembolic event within past 6 months