Clinical trial NCT02788708: Lenvatinib and Weekly Paclitaxel for Patients With Recurrent Endometrial or Ovarian Cancer
Official title: Phase I Evaluation of Lenvatinib and Weekly Paclitaxel in Patients With Recurrent Endometrial, Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fallopian Tube Carcinoma
Recurrent Ovarian Cancer
Primary Peritoneal Carcinoma
Recurrent Endometrial Cancer
Keywords: paclitaxel
lenvatinib
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
First posted: 2016-06-02
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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 (microliter)
* 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 X ULN OR creatinine clearance \>= 30 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
* Patients who have a history of deep vein thrombosis (DVT) or pulmonary embolus and are stable on anticoagulation for \> 1 month are eligible

Primary outcomes:
measure: Maximum tolerated dose (MTD) of lenvatinib mesylate when given with paclitaxel defined as the highest dose level with =< 1 dose limiting toxicities among 6 patients graded by CTCAE
timeFrame: 4 weeks
Secondary outcomes:
measure: Objective antitumor activity (complete and partial response) assessed by RECIST criteria
timeFrame: Up to 5 years
measure: Pharmacokinetics (PK) of combination paclitaxel and lenvatinib mesylate
timeFrame: Cycle 1 Day 1 and Day 15 (cycle is 28 days).
measure: Progression free survival
timeFrame: months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Floor Backes, MD
role: PRINCIPAL_INVESTIGATOR
References: