Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer

Phase 2

Completed

Conditions: Endometrial Adenocarcinoma
Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation
Endometrioid Stromal Sarcoma
Endometrial Serous Adenocarcinoma
Endometrial Adenosquamous Carcinoma
Endometrial Clear Cell Adenocarcinoma
Recurrent Uterine Corpus Carcinoma

Interventions: Biological: Trebananib

Registration Number: NCT01210222

Lead Sponsor: Gynecologic Oncology Group

Brief Summary: This phase II trial studies the side effects and how well trebananib works in treating patients with persistent or recurrent endometrial cancer. Trebananib may stop the growth of endometrial cancer by blocking blood flow to the tumor.

Detailed Description: PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with persistent or recurrent endometrial cancer, who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with AMG 386 (trebananib).

II. To determine the nature and degree of toxicity of AMG 386 in this cohort of patients.

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent endometrial cancer treated with AMG 386.

OUTLINE:

Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 35

Inclusion Criteria

Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; stained slides to document the primary tumor as well as recurrent/persistent disease (if documented by histology or cytology) are required
Patients with the following histologic epithelial cell types are eligible:
- Endometrioid adenocarcinoma
- Serous adenocarcinoma
- Undifferentiated carcinoma
- Clear cell adenocarcinoma
- Mixed epithelial carcinoma
- Adenocarcinoma not otherwise specified (N.O.S.)
- Mucinous adenocarcinoma
- Squamous cell carcinoma
- Transitional cell carcinoma
All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence >= 90 days following completion of radiation therapy
Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III or Rare Tumor protocol for the same patient population
Patients who have received one prior chemotherapy regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior chemotherapy regimens must have a GOG performance status of 0 or 1
Recovery from effects of recent surgery, radiotherapy, or chemotherapy
Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration
Any prior radiation therapy must be completed at least 4 weeks prior to registration
Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a chemotherapy regimen
Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease
Patients must have NOT received any non-cytotoxic (biologic or targeted) agents as part of their primary treatment or for management of recurrent or persistent disease
- Non-cytotoxic (biologic or targeted) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction
Prior hormonal therapy is allowed; there is no limit on the number of prior hormonal therapies allowed
Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
Platelets greater than or equal to 100,000/mcl
Hemoglobin level >= 9.0 g/dL
Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) or a creatinine clearance >= 60 ml/m^2
Bilirubin less than or equal to 1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN
Alkaline phosphatase less than or equal to 2.5 x ULN
Neuropathy (sensory and motor) less than or equal to grade 1
Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN
Albumin >= 2.8 mg/dL
Patients must have a urine protein of =< 1 on dipstick; if dipstick is 2+ or higher, 24-hour urine protein must be obtained and should be < 1 g for patient to be eligible
Patients must have signed an approved informed consent and authorization permitting release of personal health information
Patients of child bearing potential must agree to use an accepted and effective non-hormonal method of contraception i.e., double barrier method (e.g. condom plus diaphragm) from the time of signing the informed consent through 6 months after last dose of study drug

Exclusion Criteria

Patients who are currently or have been previously treated with trebananib, or other molecules that inhibit the angiopoietins or Tie2 receptor
Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
Patients who are pregnant or nursing
Patients with symptoms of partial or complete bowel obstruction; recent (within 6 months) history of fistula, intraabdominal abscess or bowel perforation; subjects requiring total parenteral nutrition or parenteral hydration
Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including brain tumor, seizures not controlled with standard medical therapy or any brain metastases
Patients with clinically significant cardiovascular disease; this includes:
- Myocardial infarction or unstable angina within 12 months of the first date of study treatment
- New York Heart Association (NYHA) Class II or greater congestive heart failure
- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
- Grade 2 or greater peripheral vascular disease
- Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study treatment
- History of arterial ischemia or thrombus
Patients with uncontrolled hypertension defined as systolic > 150 mm Hg or diastolic > 90 mm Hg; the use of anti-hypertensive medications to control hypertension is permitted
Patients with significant bleeding within 6 months of enrollment or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Patients who have undergone major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of study treatment or who have major surgical procedure anticipated during the course of the study
Patients who have undergone minor surgical procedures within 7 days of the first date of study treatment
- Paracentesis and thoracentesis are permitted prior to and while on study at the discretion of the investigator and as clinically indicated
Patients treated with immune modulators such as systemic cyclosporine or tacrolimus within 30 days prior to enrollment
Patients with serious non-healing wound, ulcer (including gastrointestinal), or bone fracture
Patients with known human immunodeficiency virus (HIV), hepatitis C or chronic or active hepatitis B
Patients with any condition which, in the investigator's opinion, makes the patient unsuitable for study participation
Patients not available for follow-up assessments
Patients with known sensitivity to any of the products to be administered during dosing
Patients with history of allergic reactions to bacterially produced proteins
Patients with a history of venous or arterial thromboembolism within 12 months prior to enrollment/randomization

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (trebananib)	Trebananib	Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival > 6 Months	At 6 months	Whether or not the patient survived progression-free for at least 6 months.
Adverse Events as Assessed by NCI CTCAE v 4.0	Up to 5 years
Objective Tumor Response (Complete or Partial Response)	Up to 5 years	Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From study entry to death or last contact, up to 5 years	The observed length of life from entry into the study to death or the date of last contact.
Progression-free Survival	Patients whose disease can be evaluated by physical exam, progression was assessed prior to each cycle. CT or MRI if used to follow leasion for measurable disease, up to 5 years	The time from entry until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Trial Locations

Locations (33): University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Sarasota Memorial Hospital
🇺🇸
Sarasota, Florida, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Memorial University Medical Center
🇺🇸
Savannah, Georgia, United States
Saint Vincent Hospital and Health Care Center
🇺🇸
Indianapolis, Indiana, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
🇺🇸
Hinsdale, Illinois, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸
Des Moines, Iowa, United States
Iowa-Wide Oncology Research Coalition NCORP
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Maine Medical Center-Bramhall Campus
🇺🇸
Portland, Maine, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States
AnMed Health Cancer Center
🇺🇸
Anderson, South Carolina, United States
Saint Francis Hospital
🇺🇸
Greenville, South Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸
Ames, Iowa, United States
Southeast Clinical Oncology Research (SCOR) Consortium NCORP
🇺🇸
Winston-Salem, North Carolina, United States