Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma
Condition: Fallopian Tube Cancer; Female Reproductive Cancer; Ovarian Carcinosarcoma; Ovarian Sarcoma; Recurrent Ovarian Epithelial Cancer; Recurrent Uterine Sarcoma; Stage III Ovarian Epithelial Cancer; Stage III Uterine Sarcoma; Stage IV Ovarian Epithelial Cancer; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma
MeSH terms: Sarcoma; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Leiomyosarcoma; Carcinosarcoma; Mixed Tumor, Mullerian; Recurrence
Intervention: ziv-aflibercept
Intervention description: Given IV
Intervention MeSH terms: Aflibercept; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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