Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-15273

Full Title

Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer

Purpose

This phase I trial studies the side effects and best dose of lenvatinib mesylate when given together with paclitaxel in treating patients with endometrial, ovarian, fallopian tube, or primary peritoneal cancer that has come back or grown. Lenvatinib mesylate may stop the growth of tumor cells by blocking a protein needed for cell growth and may block the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lenvatinib mesylate and paclitaxel together may work better in treating patients with endometrial, ovarian, fallopian tube, or primary peritoneal cancer.

Study Objective

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (RPTD) of combination lenvatinib mesylate (lenvatinib) and weekly paclitaxel in patients with recurrent endometrial, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of combination lenvatinib and weekly paclitaxel in patients with recurrent endometrial, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.

II. To explore the objective antitumor activity (complete and partial response) of combination lenvatinib and weekly paclitaxel as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

III. To measure the progression free survival.

IV. To evaluate the pharmacokinetics of combination paclitaxel and lenvatinib.

OUTLINE: This is a dose -escalation study of lenvatinib mesylate.

Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and lenvatinib mesylate orally (PO) once daily (QD) on days 1-28. 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 3 months for 3 years.

Are you eligible?

Inclusion Criteria:

Patients must have histologically confirmed endometrial cancer, epithelial ovarian, fallopian tube, or primary peritoneal cancer (all histologic subtypes)

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 cancer can be platinum-sensitive (with documented progression > 6 months after completion of a platinum containing regimen) or 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

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

Patients who have a history of deep vein thrombosis or pulmonary embolus and are stable on anticoagulation for > 1 month are eligible

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

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:

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%)

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 (ie, 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

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

Hemoptysis or other pulmonary bleeding > grade 2

Hematuria or other genitourinary bleeding > grade 2

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

Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy

Ovarian Cancer Gynecologic Cancers