This trial is active, not recruiting.

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
Treatments ziv-aflibercept, laboratory biomarker analysis, pharmacological study
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date September 2006
End date September 2011
Trial size 82 participants
Trial identifier NCT00390234, CDR0000508798, N01CM62201, N01CM62203, N01CM62209, NCI-2009-00177, PHL-051


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Patients receive ziv-aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
ziv-aflibercept aflibercept
Given IV
laboratory biomarker analysis
Correlative studies
pharmacological study pharmacological studies
Correlative studies

Primary Outcomes

Objective response rate, evaluated according to the RECIST criteria
time frame: Up to 3 years
Incidence of disease stabilization, as measured by progression-free survival at 6 months
time frame: 6 months

Secondary Outcomes

time frame: Up to 3 years
Response as assessed by RECIST criteria
time frame: Up to 3 years

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed soft tissue sarcoma of the gynecologic tract, including 1 of the following subtypes: uterine leiomyosarcoma, malignant mixed mullerian tumor/carcinosarcoma, disease originating in the ovary or fallopian tube allowed - Locally advanced, unresectable, or metastatic disease - Previously treated disease must have radiographic or clinical evidence of progressive disease - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan - Indicator lesions may not have been previously treated with surgery, radiotherapy, or radiofrequency ablation unless progressive disease has been confirmed - No evidence of CNS disease, including primary brain tumor or brain metastasis - ECOG performance status (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 =< 1.5 times upper limit of normal (ULN) - AST and ALT =< 3 times ULN - INR =< 1.5 (unless on warfarin) - Creatinine =< 1.5 times ULN 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 or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment - No other active malignancy within the past 5 years except adequately treated cervical carcinoma in situ or nonmelanoma skin cancer - No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies - No history of allergic reactions attributed to compounds of similar chemical or biological composition to study agents - No serious or nonhealing wound, ulcer, or bone fracture - No abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within the past 28 days - No significant traumatic injuries within the past 28 days - No clinically significant cardiovascular disease, including any of the following: - Cerebrovascular accident within the past 6 months, - Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg OR systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg, on ≥ 2 repeated determinations on separate days within the past 3 months, - OR; Antihypertensive medications allowed, as long as the dose and number of antihypertensive medications have not been increased within the past 2 weeks, Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months, OR; - OR; New York Heart Association class III-IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris within the past 6 months, Clinically significant peripheral vascular disease within the past 6 months (i.e., limiting activities of daily living or the presence of pain at rest), - OR; pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months - No evidence of bleeding diathesis or coagulopathy - No uncontrolled intercurrent illness including, but not limited to, the following: Ongoing or active infection, psychiatric illness or social situations that would preclude study compliance - No more than 2 prior cytotoxic chemotherapy regimen for recurrent, locally advanced, or metastatic disease - Recovered from prior therapy - No prior antiangiogenic agent - At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin C) - At least 4 weeks since prior investigational treatment - At least 4 weeks since prior radiotherapy - At least 4 weeks since prior major surgery or open biopsy - At least 1 week since prior core biopsy - At least 1 month since prior thrombolytic agents - Concurrent full-dose anticoagulants (e.g., warfarin) with INR > 1.5 allowed provided all the following criteria are met:, In-range INR (usually between 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, - OR; For patients on warfarin, the upper target for INR is ≤ 3 No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor invading major vessels or known varices) - No other concurrent investigational agents - No concurrent major surgery - No concurrent combination antiretroviral therapy for HIV-positive patients

Additional Information

Official title A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas
Principal investigator Amit Oza
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).