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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00390234
First received: October 18, 2006
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: ziv-aflibercept
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate, evaluated according to the RECIST criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of disease stabilization, as measured by progression-free survival at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Survival statistics will be estimated using the Kaplan-Meier method. Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. 95% confidence intervals will be provided for estimates of interest where possible.

  • Response as assessed by RECIST criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. 95% confidence intervals will be provided for estimates of interest where possible.


Estimated Enrollment: 82
Study Start Date: September 2006
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ziv-aflibercept)
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.
Drug: ziv-aflibercept
Given IV
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390234

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
University of Southern California
Los Angeles, California, United States, 90033-0804
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Evanston CCOP-NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Peoria Gynecologic Oncology
Peoria, Illinois, United States, 61603
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
United States, Pennsylvania
Fox Chase Cancer Center
Rockledge, Pennsylvania, United States, 19046
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5C 1M9
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University Department of Oncology
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
Investigators
Principal Investigator: Amit Oza University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00390234     History of Changes
Other Study ID Numbers: NCI-2009-00177, PHL-051, CDR0000508798, N01CM62209, N01CM62203, N01CM62201
Study First Received: October 18, 2006
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uterine Neoplasms
Adnexal Diseases
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Gonadal Disorders
Ovarian Diseases
Uterine Diseases
Carcinosarcoma
Fallopian Tube Neoplasms
Leiomyosarcoma
Mixed Tumor, Mullerian
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Sarcoma
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Urogenital Neoplasms
Endothelial Growth Factors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 30, 2014