Clinical trial NCT00462826: VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer
Official title: A Phase II Evaluation of VEGF-Trap (AFLIBERCEPT, NSC #724770, NCI-Supplied Agent) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Endometrial Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2007-04-19
Enrollment: 49
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 6 Month Progression-free Survival
timeFrame: At 6 monthsEvery other cycle during treatment for the first 6 months.
measure: Objective Tumor Response (RECIST 1.0)
timeFrame: 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.
measure: 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
timeFrame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Secondary outcomes:
measure: Duration of Progression-free Survival
timeFrame: 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.
measure: Duration of Overall Survival
timeFrame: 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.
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Jupiter
country: United States
facility: Jupiter Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Services
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Olathe
country: United States
facility: Radiation Oncology Center of Olathe
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Radiation Oncology Practice Corporation Southwest
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Franklin Square Hospital Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Escanaba
country: United States
facility: Green Bay Oncology - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology - Iron Mountain
state: Michigan
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation South
state: Missouri
city: Kansas City
country: United States
facility: Saint Joseph Health Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation - North
state: Missouri
city: Liberty
country: United States
facility: Liberty Hospital
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Southwest Gynecologic Oncology Associates Inc
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Gynecologic Oncology Network
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health Center West
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Mentor
country: United States
facility: Lake University Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates-Midtown
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Cancer Institute
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Roanoke
country: United States
facility: Carilion Clinic Gynecological Oncology
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties PLLC
state: Washington
city: Green Bay
country: United States
facility: Green Bay Oncology at Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology Limited at Saint Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Mary's Hospital
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Gynecologic Oncology Group
name: Robert Coleman
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.