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A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas

Phase 2
18 Years
Open (Enrolling)
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

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Trial Information

A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas


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.


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.

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

- Locally advanced, unresectable, or metastatic disease

- Previously treated disease must have radiographic or clinical evidence of progressive

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate, evaluated according to the RECIST criteria

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Amit Oza

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network-Princess Margaret Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

September 2006

Completion Date:

Related Keywords:

  • 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
  • Carcinosarcoma
  • Mixed Tumor, Mullerian
  • Leiomyosarcoma
  • Fallopian Tube Neoplasms
  • Uterine Neoplasms
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Sarcoma



Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
City of Hope Duarte, California  91010
UC Davis Comprehensive Cancer Center Sacramento, California  95817
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
University of Southern California Los Angeles, California  90033
Evanston CCOP-NorthShore University HealthSystem Evanston, Illinois  60201
University of Michigan University Hospital Ann Arbor, Michigan  48109
Peoria Gynecologic Oncology Peoria, Illinois  61603