ziv-aflibercept in treating patients with locally advanced, unresectable, or metastatic gynecologic soft tissue sarcoma

Conditions: 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

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.

primary objectives: i. to assess the objective response of recurrent or metastatic gynecologic soft-tissue sarcomas to vegf-trap (ziv-aflibercept). ii. to assess the incidence of disease stabilization, as measured by 6-month progression-free survival, in patients with recurrent or metastatic gynecologic soft-tissue sarcomas treated with vegf-trap. secondary objectives: i. to assess time-to-progression and overall survival in patients with recurrent or metastatic gynecologic soft-tissue sarcoma treated with vegf-trap. \* as of 24 october 2012, overall survival follow-up is to be discontinued for the one remaining patient on long term follow-up, who has been off protocol therapy for at least 3 years. time to progression and median survival times have been based on the currently available data. ii. to assess the toxicity associated with vegf-trap in patients with recurrent or metastatic gynecologic soft-tissue sarcoma. iii. to characterize the population pharmacokinetics of vegf-trap and to explore for demographic and clinical covariates outline: this is an open-label, multicenter study. patients are stratified according to histology (uterine leiomyosarcoma vs malignant mixed mullerian tumor/carcinosarcoma). patients receive ziv-aflibercept over 1 hour on day 1. treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. patients undergo blood collection at baseline, every 8 weeks during treatment, and 60 days after completion of study treatment for population pharmacokinetic analysis using enzyme-linked immunosorbent assay (elisa). after completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

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=\ =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