Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma
Primary Purpose
Fallopian Tube Cancer, Female Reproductive Cancer, Ovarian Carcinosarcoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ziv-aflibercept
Sponsored by
About this trial
This is an interventional treatment trial for Fallopian Tube Cancer
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
Sites / Locations
- City of Hope
- University of Southern California
- UC Davis Comprehensive Cancer Center
- University of Chicago Comprehensive Cancer Center
- Evanston CCOP-NorthShore University HealthSystem
- Peoria Gynecologic Oncology
- University of Michigan University Hospital
- Fox Chase Cancer Center
- Vancouver General Hospital
- BCCA-Vancouver Cancer Centre
- Juravinski Cancer Centre at Hamilton Health Sciences
- Cancer Centre of Southeastern Ontario at Kingston General Hospital
- London Regional Cancer Program
- Odette Cancer Centre- Sunnybrook Health Sciences Centre
- University Health Network-Princess Margaret Hospital
- McGill University Department of Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (ziv-aflibercept)
Arm Description
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.
Outcomes
Primary Outcome Measures
Objective Response Rate, Evaluated According to the RECIST Criteria
Incidence of Disease Stabilization, as Measured by Progression-free Survival at 6 Months (Leiomyosaroma Group)
Incidence of Disease Stabilization, as Measured by Progression-free Survival at 6 Months (Carcinosarcoma Group)
Secondary Outcome Measures
Survival (Leiomyosarcoma Group)
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.
Survival (Carcinosarcoma Group)
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.
Full Information
NCT ID
NCT00390234
First Posted
October 18, 2006
Last Updated
December 3, 2015
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00390234
Brief Title
Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma
Official Title
A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (ziv-aflibercept)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ziv-aflibercept
Other Intervention Name(s)
aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Objective Response Rate, Evaluated According to the RECIST Criteria
Time Frame
Up to 3 years
Title
Incidence of Disease Stabilization, as Measured by Progression-free Survival at 6 Months (Leiomyosaroma Group)
Time Frame
6 months
Title
Incidence of Disease Stabilization, as Measured by Progression-free Survival at 6 Months (Carcinosarcoma Group)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Survival (Leiomyosarcoma Group)
Description
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.
Time Frame
Up to 3 years
Title
Survival (Carcinosarcoma Group)
Description
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.
Time Frame
Up to 3 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Oza
Organizational Affiliation
University Health Network-Princess Margaret Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033-0804
Country
United States
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Evanston CCOP-NorthShore University HealthSystem
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Peoria Gynecologic Oncology
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61603
Country
United States
Facility Name
University of Michigan University Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Fox Chase Cancer Center
City
Rockledge
State/Province
Pennsylvania
ZIP/Postal Code
19046
Country
United States
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5C 1M9
Country
Canada
Facility Name
BCCA-Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Odette Cancer Centre- Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
McGill University Department of Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma
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