VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Phase II Evaluation of VEGF-Trap (AFLIBERCEPT, NSC #724770, NCI-Supplied Agent) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Endometrial Carcinoma
• Intervention / Treatment: Biological: ziv-aflibercept

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • Georgia
    • Savannah, Georgia, United States, 31403
      • Memorial Health University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Services
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University Of Iowa Hospitals And Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66112
      • Providence Medical Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Olathe, Kansas, United States, 66061
      • Radiation Oncology Center of Olathe
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66210
      • Radiation Oncology Practice Corporation Southwest
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology - Escanaba
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
  • Missouri
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute
    • Kansas City, Missouri, United States, 64114
      • Saint Joseph Health Center
    • Kansas City, Missouri, United States, 64114
      • Radiation Oncology Practice Corporation South
    • Kansas City, Missouri, United States, 64154
      • Radiation Oncology Practice Corporation - North
    • Liberty, Missouri, United States, 64068
      • Liberty Hospital
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Southwest Gynecologic Oncology Associates Inc
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Greenville, North Carolina, United States, 27834
      • Gynecologic Oncology Network
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Institute
    • Tulsa, Oklahoma, United States, 74104
      • Cancer Care Associates-Midtown
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Carilion Clinic Gynecological Oncology
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (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.	Biological: ziv-aflibercept; Other Names: aflibercept; vascular endothelial growth factor trap; VEGF Trap; Zaltrap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Month Progression-free Survival	Number of participants who survived progression-free for more than 6 months.	At 6 monthsEvery other cycle during treatment for the first 6 months.
Objective Tumor Response (RECIST 1.0)	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.	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.
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	Adverse events at least possibly related to the study agent.	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Progression-free Survival	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.	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.
Duration of Overall Survival	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	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.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group
• Investigators: Principal Investigator: Robert Coleman, Gynecologic Oncology Group

Publications and helpful links

General Publications

• Coleman RL, Sill MW, Lankes HA, Fader AN, Finkler NJ, Hoffman JS, Rose PG, Sutton GP, Drescher CW, McMeekin DS, Hu W, Deavers M, Godwin AK, Alpaugh RK, Sood AK. A phase II evaluation of aflibercept in the treatment of recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2012 Dec;127(3):538-43. doi: 10.1016/j.ygyno.2012.08.020. Epub 2012 Aug 23. Erratum In: Gynecol Oncol. 2013 Jul;130(1):252-3.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: April 18, 2007
• First Submitted That Met QC Criteria: April 18, 2007
• First Posted (Estimate): April 19, 2007

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Disease Attributes; Carcinoma; Recurrence; Endometrial Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-00597 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000540237; GOG-0229F (Other Identifier: CTEP)