Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Endometrioid Stromal Sarcoma; Recurrent Uterine Corpus Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous; Sarcoma, Endometrial Stromal; Recurrence
Intervention: Trebananib
Intervention description: Given IV
Intervention MeSH terms: Trebananib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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