VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer

Recurrent Endometrial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00462826
• Other study ID #: NCI-2009-00597
• Secondary ID: NCI-2009-00597CD
• Status: Completed
• Phase: Phase 2
• Start date: November 2007
• Est. completion date: January 2013

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Endometrial Neoplasms
• Recurrent Endometrial Carcinoma

Intervention

Biological:
• ziv-aflibercept

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Gynecologic Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.