Lenvatinib Mesylate and Paclitaxel in Treating Patients with Recurrent Endometrial, Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Inclusion Criteria

• Women with histologically confirmed endometrial cancer, epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer (all histological subtypes) who have disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to prior treatment
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computerized tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have received prior treatment with a platinum containing regimen and may have received an unlimited number of prior regimens (including prior taxanes)
• Patients with ovarian, fallopian tube or primary peritoneal cancer must be platinum resistant (progression < 6 months after completion of a platinum containing regimen)
• Patients may have received prior targeted therapy such as bevacizumab
• Eastern Cooperative Oncology Group performance status =< 1
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8.0 g/dL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
• Creatinine < 1.5 mg/dL OR creatinine clearance >= 50 mL/min for patients with creatinine levels above institutional normal
• Urine protein by dipstick <1+ or UPC =< 1.0 by urinalysis
• Patients with chronic hypertension that is well controlled with systolic blood pressure of < 140 mmHg or diastolic blood pressure of < 90 mmHg, and in whom there has been no change in blood pressure medication in the last two weeks, are eligible
• Although extremely rare in this population that fertility would still be an option, a female is eligible to participate if she is of non-childbearing potential or has documentation of a negative pregnancy test prior to the start of the study treatment; sexually active pre-menopausal female subjects of child-bearing potential must agree to use adequate, highly effective contraceptive measures, while on study and for 45 days after the last dose of last study drug; effective birth control includes: intrauterine device (IUD) plus one barrier method; oral, implantable or injectable contraceptives plus one barrier method; 2 barrier methods; effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients must have recovered from all adverse events > grade 1 (except grade 2 alopecia and grade 2 fatigue) due to prior chemotherapy or radiotherapy and may not have received any radiotherapy within 3 weeks or any chemotherapy within 3 weeks or 5 half-lives whichever is longer prior to study entry; patients may not have received biologics, targeted therapy or immunotherapy for 3 weeks
• Patients who are currently receiving any other investigational agents.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib and/or paclitaxel
• Concomitant use of cytochrome P450 (CYP3A4) inhibitors or inducers is allowed but should be monitored closely for the use of strong inhibitors and/or inducers; patient is strongly advised to avoid grapefruit or grapefruit juice and herbal supplements with high risk of interaction with CYP3A4 or CYP2C8, such as St. John’s Wort while on study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Significant cardiovascular disease, including: * If the patient has a known history of decreased left ventricular ejection fraction (LVEF) on imaging or clinical suggestion of heart failure, an echocardiogram (ECHO) or multigated acquisition scan (MUGA) should be completed; symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of < lower limit of institutional normal (LVEF<50%) will exclude the patient * Patients with marked baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females) * Uncontrolled hypertension: systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart * Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug * History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) * Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication) * Coronary or peripheral artery bypass graft within 6 months of screening * History of class III or IV congestive heart failure as defined by the New York Heart Association
• Major surgical procedure (e.g. laparotomy, bowel resection) 4 weeks prior to start of the study drug
• Central nervous system metastasis; Note: patients with previously treated (radiotherapy or surgery) brain metastasis that have been stable without steroid treatment for at least 3 months following prior treatment may be enrolled
• Neuropathy grade >1
• Non-healing wound, bone fracture, or skin ulcer
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
• Patients who have a history of a small or large bowel obstruction within 2 weeks of screening or who have and active partial small bowel obstruction or percutaneous endoscopic gastrostomy (PEG)-tube
• Serious/active infection or infection requiring parenteral antibiotics
• Significant arterial or venous thromboembolic disease or vascular disorders within 6 months prior to administration of first dose of study drug, including by not limited to: * Cerebrovascular accident (CVA) or transient ischemic attack (TIA) * Peripheral ischemia > grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) * Arterial thrombotic event
• Patients who have a history of deep vein thrombosis or pulmonary embolus < 3 months prior to enrollment must be excluded; however, if patients are on therapeutic anticoagulation, and the deep vein thrombosis/pulmonary embolism (DVT/PE) has been clinically stable or improved on anticoagulation for >3 months, patients are eligible
• Patients with a history of clotting disorders must be excluded
• Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to: * Hematemesis, hematochezia, melena or other gastrointestinal bleeding >= grade 2 (per CTCAE version 4.03) * Hemoptysis or other pulmonary bleeding >= grade 2 (per CTCAE version 4.03) * Hematuria or other genitourinary bleeding >= grade 2 (per CTCAE version 4.03)
• Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
• Patients with other malignancies within 5 years from enrollment, with the exception of non-melanoma skin cancer, cervix in situ
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated lenvatinib
• Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy