Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm; Recurrent Uterine Corpus Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence
Intervention: Nintedanib
Intervention description: Given PO
Intervention MeSH terms: Nintedanib; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well nintedanib works in treating
      patients with endometrial cancer that has come back. Nintedanib may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth or 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; 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 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

          -  Patient 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 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 must have a GOG performance status of 0, 1, or 2

          -  Patients must have normal thyroid function; patients with a history of hypothyroidism
             are eligible, provided it is well controlled on medication

          -  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)

          -  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 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) 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

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

          -  Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection
             of 24-hour urine measurement of urine protein is recommended

          -  Bilirubin must be less than 1.5 X ULN

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than
             3 X ULN

          -  Alkaline phosphatase must be less than 2.5 X ULN

          -  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 times the
             institutional upper limit of normal

          -  Electrocardiogram (EKG) must have corrected QT interval (QTc) < 450 msec without
             evidence of serious ventricular arrhythmia (ventricular tachycardia lasting more than
             3 beats or ventricular fibrillation)

          -  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; women of child-bearing potential must agree to use adequate
             contraception (two barrier methods of birth control) prior to study entry and for the
             duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she is to inform her treating physician
             immediately; all patients must be willing to take contraception up to three months
             after the final dose of BIBF 1120

        Exclusion Criteria:

          -  Patients who have had prior therapy with BIBF 1120

          -  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 serious, non-healing wound, ulcer, or bone fracture; this includes
             history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 28 days prior to the start date of treatment; patients with underlying lesions
             that caused the fistula or perforation in the past that have not been corrected

          -  Patients with active bleeding or pathologic conditions that carry high risk of
             bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
             vessels

          -  Patients with history of brain metastases, or evidence upon physical examination of
             active central nervous system (CNS) disease, including primary brain tumor, seizures
             not controlled with standard medical therapy or any brain metastases

          -  Uncontrolled hypertension, defined as systolic >= 150 mm Hg or diastolic >= 90 mm Hg

          -  Myocardial infarction or unstable angina within 6 months of study treatment

          -  New York Heart Association (NYHA) class II or greater congestive heart failure

          -  Women with an ejection fraction < institutional lower limit of normal (LLN)

          -  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)

          -  Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral
             vascular disease

          -  History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or
             subarachnoid hemorrhage within six months of study treatment

          -  Patients undergoing invasive procedures as defined below: major surgical procedure,
             open biopsy or significant traumatic injury within 28 days prior to the first date of
             treatment; major surgical procedure anticipated during the course of the study; minor
             surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to
             the first date of therapy

          -  Patients who are pregnant or nursing

          -  Patients with a history of major thromboembolic event defined as: symptomatic
             pulmonary embolism (PE), recurrent asymptomatic PE, or recurrent deep venous
             thrombosis

          -  Prior thrombosis or thromboembolic event due to a known inherited coagulopathy (i.e.,
             antithrombin-III deficiency, protein C or protein S deficiency, factor V Leiden
             mutation presence, prothrombin G20210A mutation)

          -  Serious infections requiring systemic antibiotics or antiviral therapy including:
             known active hepatitis B or C infection; known human immunodeficiency virus (HIV)
             infection

          -  Gastrointestinal (GI) or other medical disorders that would impact ingestion or
             absorption of the drug

          -  Patients with a history of photosensitivity or who must take agents which increase
             photosensitivity, e.g. topical retinoids and doxycycline

          -  Patients who are unable to swallow capsules