Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence
Intervention: Dalantercept; Laboratory Biomarker Analysis
Intervention description: Given SC; Correlative studies
Intervention MeSH terms: Immunoglobulin Fc Fragments
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well dalantercept works in treating patients with endometrial
      cancer that has come back or is persistent. Dalantercept 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; histologic
             confirmation of the original primary tumor is 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,
                  and transitional cell carcinoma

          -  All patients must have measurable disease; measurable disease is defined by Response
             Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) 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 version 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 at least 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
             protocol or rare tumor protocol for the same patient population

          -  Patients who have received one prior regimen must have a GOG performance status of 0,
             1, or 2; patients who have received two prior 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 investigational drug must be discontinued at least 30 days
                  prior to registration

               -  Any prior radiation therapy must be discontinued at least four weeks prior to
                  registration

               -  At least 4 weeks must have elapsed since the patient underwent any major surgery
                  (e.g., major: laparotomy, laparoscopy); there is no delay in treatment for minor
                  procedures (e.g., central venous access catheter placement)

          -  Prior therapy

               -  Patients must have had one prior chemotherapeutic regimen for management of
                  endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy
                  and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy
                  administered in conjunction with primary radiation as a radio-sensitizer WILL be
                  counted as a systemic 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) agent(s)
                  for management of recurrent or persistent disease; prior non-cytotoxic (biologic
                  or targeted) agent(s) is allowed as part of initial treatment; prior hormonal
                  therapy is allowed, but must be discontinued at least one week prior to
                  registration

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL

          -  Platelets greater than or equal to 100,000/mcL

          -  Hemoglobin greater than or equal to 9 g/dL

          -  Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN)

          -  Sodium greater than or equal to 130 mEq/L (Common Terminology Criteria for Adverse
             Events [CTCAE] v. 4, grade 0 or 1)

          -  Urine protein should be screened by urinalysis; if protein is 2+ or higher, 24-hour
             urine protein should be obtained and the level should be < 1,000 mg (< 1.0 g/24 hrs)
             for patient enrollment

          -  Bilirubin less than or equal to 1.5 times ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
             to 3 times ULN

          -  Alkaline phosphatase less than or equal to 3 times ULN

          -  Albumin greater than or equal to 3 (CTCAE v. 4, grade 0 or 1)

          -  Prothrombin time (PT) such that international normalized ratio (INR) is less than or
             equal to 1.5 times ULN (or an in-range INR, usually between 2 and 3, if a patient is
             on a stable dose of therapeutic warfarin)

          -  Partial thromboplastin time (PTT) less than or equal to 1.5 times ULN

          -  Left ventricular ejection fraction (LVEF) greater than 50% (measured by echocardiogram
             or MUGA [multi-gated acquisition] scan)

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must meet pre-entry requirements

          -  Patients of childbearing potential must have a negative serum pregnancy test prior to
             the study entry and be practicing an effective form of contraception

        Exclusion Criteria:

          -  Patients who have had prior therapy with dalantercept or other inhibitor of the ALK1
             pathway

          -  Patients 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 with history or evidence upon physical exam of central nervous system disease
             (CNS) disease, including primary brain tumor, seizures not controlled with standard
             medical therapy, or any brain metastases or leptomeningeal disease

          -  Serious or non-healing wound, ulcer, or bone fracture

          -  History of abdominal fistula or anastomotic leak, gastrointestinal perforation, or
             intra-abdominal abscess within 6 months of registration

          -  Patients requiring parenteral hydration or parenteral/total parenteral nutrition

          -  No patients with:

               -  Active bleeding (e.g., active hemoptysis, defined as bright red blood of greater
                  than or equal to ½ teaspoon [2.5 ml] in any 24-hour period) within 2 weeks prior
                  to registration or gastrointestinal bleeding within 3 months prior to
                  registration

               -  Hereditary hemorrhagic telangiectasia (HHT)

               -  Platelet function abnormality

               -  Autoimmune or hereditary hemolysis

               -  Coagulopathy, or

               -  Tumor involving major vessels (defined as any lesion invading or abutting the
                  wall [i.e., no fat plane evident] of major blood vessels as assessed by CT or
                  MRI)

          -  Patients receiving treatment with full-dose aspirin (325 mg oral daily), clopidogrel
             (Plavix), or dabigatran (Pradaxa)

          -  Patients with peripheral edema greater than or equal to grade 1 within 4 weeks of
             registration

          -  No patients with clinically significant cardiovascular disease:

               -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm
                  Hg despite antihypertensive medications

               -  Evidence of hypertrophic cardiomyopathy

               -  New York Heart Association (NYHA) class II or greater congestive heart failure
                  (CHF)

               -  Any of the following within 6 months prior to study registration:

                    -  Bypass surgery

                    -  Stent placement

                    -  Myocardial infarction

                    -  Acute coronary syndrome/unstable angina

                    -  Hospitalization for congestive heart failure (CHF)

               -  Serious cardiac arrhythmia requiring medication; this does not include
                  asymptomatic atrial fibrillation with controlled ventricular rate

               -  Prolonged QTc interval > 450 ms

               -  Prior anthracycline cumulative dose > 450 mg/m^2

          -  Patients who are pregnant or nursing

          -  History of syndrome of inappropriate antidiuretic hormone secretion (SIADH)

          -  Patients who have undergone a therapeutic paracentesis within 4 weeks of registration

          -  Known history of positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV)
             surface antigen (HBsAg), or HBV core antibody, or human immunodeficiency virus (HIV)
             antibody results

          -  History of severe (National Cancer Institute-Common Terminology Criteria for Adverse
             Events [NCI-CTCAE] v.4.0 >= grade 3) allergic or anaphylactic reaction or
             hypersensitivity to recombinant proteins or excipients (10 mM Tris buffered saline) in
             the investigational agent

          -  Clinically significant active pulmonary risk including pulmonary hypertension,
             pulmonary embolism, or history of pulmonary edema