VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer

Phase 2

Completed

Conditions: Recurrent Endometrial Carcinoma

Interventions: Biological: ziv-aflibercept

Registration Number: NCT00462826

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent or persistent endometrial cancer. VEGF Trap may stop the growth of endometrial cancer by blocking blood flow to the tumor and by carrying tumor-killing substances directly to endometrial cancer cells.

Detailed Description: PRIMARY OBJECTIVES:

I. Assess the activity of VEGF Trap in patients with recurrent or persistent endometrial cancer, in terms of the frequency of patients who have progression-free survival for at least 6 months after initiating therapy or have objective tumor response.

II. Determine the toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the duration of progression-free survival and overall survival of patients treated with this drug.

OUTLINE:

Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 49

Inclusion Criteria

Histologically confirmed endometrial carcinoma, meeting both of the following criteria:
- Recurrent or persistent disease
- Refractory to curative therapy or established treatments
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- Tumors within a previously irradiated field are designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days after completion of radiotherapy
Must have received one prior chemotherapeutic regimen for management of endometrial carcinoma (initial treatment may include high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment)
Not a candidate for a higher priority GOG protocol
No history or evidence of primary brain tumor or brain metastases
GOG performance status (PS) 0-2 (patients who received 1 prior regimen) OR GOG PS 0-1 (patients who received 2 prior regimens)
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Urine protein:creatinine ratio < 1.0 OR urine protein < 1.0 g by 24-hour urine collection
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
SGOT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
PT/PTT/INR ≤ 1.5 times ULN
- In-range INR (between 2 and 3) allowed if patient is on a stable dose of therapeutic warfarin
QTc < 500 msec
No evidence of serious ventricular arrhythmia
- Ventricular tachycardia or ventricular fibrillation must be < 3 beats in a row
LVEF normal
- Ejection fraction ≥ 50% (for patients who received prior anthracycline, including doxorubicin hydrochloride and/or doxorubicin hydrochloride liposome)
No clinically significant cardiovascular disease, including any of the following:
- Uncontrolled hypertension, defined as systolic blood pressure (BP) > 140 mm Hg or diastolic BP > 90 mm Hg
- Myocardial infarction or unstable angina within the past 6 months
- NYHA class II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Peripheral vascular disease ≥ grade 2
- Cerebrovascular accident (i.e., CVA or stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
No HIV positivity
No neuropathy (sensory and motor) > grade 1
No active infection requiring antibiotics
No other invasive malignancies or any evidence of other cancer within the past 5 years except for nonmelanoma skin cancer
No serious nonhealing wound, ulcer, or bone fracture
No history of abdominal fistula or gastrointestinal perforation
No history or evidence of seizures not controlled with standard medical therapy
No intra-abdominal abscess within the past 28 days
No active bleeding or pathologic conditions that carry a high risk of bleeding (e.g., bleeding disorder, coagulopathy, or tumor involving major vessels)
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
No significant traumatic injury within the past 28 days
No concurrent combination antiretroviral therapy for HIV-positive patients
Recovered from prior surgery
More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
At least 1 week since prior hormonal therapy
- Concurrent hormone replacement therapy allowed
At least 3 weeks since any other prior therapy, including immunologic agents
One additional prior cytotoxic regimen for management of recurrent or persistent endometrial cancer allowed
- Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
More than 28 days since prior major surgery or open biopsy
More than 7 days since prior minor surgery, fine needle aspirates, or core biopsies
No prior cancer treatment that would preclude study compliance
No prior noncytotoxic chemotherapy for management of recurrent or persistent endometrial disease
No prior VEGF Trap or other VEGF pathway-targeted therapy
More than 5 years since prior radiotherapy to any portion of the abdominal cavity or pelvis except for the treatment of endometrial cancer
- More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin
  - Patient must remain free of recurrent or metastatic disease
More than 5 years since prior chemotherapy for any abdominal or pelvic tumor except for the treatment of endometrial cancer
- More than 3 years since prior adjuvant chemotherapy for localized breast cancer
  - Patient must remain free of recurrent or metastatic disease
Concurrent low-molecular weight heparin allowed for the prevention or treatment of venous thromboembolic disease if condition is considered clinically stable with treatment
No other concurrent investigational agents
No concurrent major surgery

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (aflibercept)	ziv-aflibercept	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Objective Tumor Response (RECIST 1.0)	Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years.	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
6 Month Progression-free Survival	At 6 monthsEvery other cycle during treatment for the first 6 months.	Number of participants who survived progression-free for more than 6 months.
Number of Participants With Incidence of Adverse Events at Least Possibly Related to Study Agent as Assessed by Common Terminology Criteria for Adverse Events Version 3.0	Assessed every cycle while on treatment, 30 days after the last cycle of treatment	Adverse events at least possibly related to the study agent.

Secondary Outcome Measures

Name	Time	Method
Duration of Progression-free Survival	Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years.	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Duration of Overall Survival	Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Trial Locations

Locations (67): Franklin Square Hospital Center
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Mount Carmel Health Center West
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Columbus, Ohio, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
University of Chicago
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Chicago, Illinois, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Saint Vincent Hospital and Health Services
🇺🇸
Indianapolis, Indiana, United States
Shawnee Mission Medical Center
🇺🇸
Shawnee Mission, Kansas, United States
Radiation Oncology Center of Olathe
🇺🇸
Olathe, Kansas, United States
Providence Medical Center
🇺🇸
Kansas City, Kansas, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
Radiation Oncology Practice Corporation Southwest
🇺🇸
Overland Park, Kansas, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Jupiter Medical Center
🇺🇸
Jupiter, Florida, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
University of Illinois
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Chicago, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
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Iowa City, Iowa, United States
Green Bay Oncology - Iron Mountain
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Iron Mountain, Michigan, United States
Green Bay Oncology - Escanaba
🇺🇸
Escanaba, Michigan, United States
Centerpoint Medical Center LLC
🇺🇸
Independence, Missouri, United States
Liberty Hospital
🇺🇸
Liberty, Missouri, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
Southwest Gynecologic Oncology Associates Inc
🇺🇸
Albuquerque, New Mexico, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Gynecologic Oncology Network
🇺🇸
Greenville, North Carolina, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
Lake University Ireland Cancer Center
🇺🇸
Mentor, Ohio, United States
Tulsa Cancer Institute
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Tulsa, Oklahoma, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Cancer Care Associates-Midtown
🇺🇸
Tulsa, Oklahoma, United States
Carilion Clinic Gynecological Oncology
🇺🇸
Roanoke, Virginia, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States
Northwest Medical Specialties PLLC
🇺🇸
Tacoma, Washington, United States
Green Bay Oncology at Saint Vincent Hospital
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Green Bay, Wisconsin, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Green Bay Oncology Limited at Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Green Bay Oncology - Oconto Falls
🇺🇸
Oconto Falls, Wisconsin, United States
Green Bay Oncology - Sturgeon Bay
🇺🇸
Sturgeon Bay, Wisconsin, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Truman Medical Center
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Cancer Institute
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Radiation Oncology Practice Corporation South
🇺🇸
Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸
Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Radiation Oncology Practice Corporation - North
🇺🇸
Kansas City, Missouri, United States