Eribulin Mesylate in Treating Patients With Advanced or Recurrent Cervical Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well eribulin mesylate works in treating patients with advanced or recurrent cervical cancer. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the activity of eribulin (eribulin mesylate) in the management of advanced or recurrent cervical cancer (progression-free survival [PFS]. SECONDARY OBJECTIVES: I. To describe the toxicity profile of eribulin in patients with advanced or recurrent cervical cancer. II. To estimate the survival of patients with advanced or recurrent cervical cancer treated with eribulin. III. To evaluate potential correlative studies as predictive or prognostic makers in this patient population (glucose-regulated protein 78 [GRP78] levels in tissue and blood, tumor protein p53 [p53] expression, apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] assay, apoptosis-related proteins B-cell lymphoma 2 [Bcl-2] and Bcl2-associated X protein [Bax] using immunohistochemistry [IHC], proliferation with Ki-67 IHC, and expression levels of microtubule-associated variables, including tau protein, total alpha- and beta-tubulin, and classes II-IV beta-tubulin isotopes with IHC. OUTLINE: Patients receive eribulin mesylate 1.4 mg/m2 intravenously (IV) bolus over 2-5 minutes on days 1 and 8. Courses repeat every 21 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.

Official Title
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Phase II Clinical Trial of Eribulin in Advanced or Recurrent Cervical Cancer

Conditions
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Stage IVB Cervical Cancer, Recurrent Cervical Cancer, Stage IIIA Cervical Cancer, Stage IIIB Cervical Cancer, Stage IVA Cervical Cancer

Intervention / Treatment
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* Drug: eribulin mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of invasive cervical cancer Measurable disease 0-1 prior chemotherapy regimens for recurrent or advanced disease; platinum based chemotherapy administered as a radiation sensitizer agent is allowed and does not count as prior therapy Absolute granulocyte count (AGC) >= 1,500 Platelet >= 100,000 Serum creatinine < 2.0 mg/dl Bilirubin =< 1.5 times the upper limit of the normal range (ULN) Alkaline phosphatase =< 3 x ULN (in the case of liver metastases, =< 5 x ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (in the case of liver metastases, =< 5 x ULN) Peripheral neuropathy grade 0-2 Recovery of all chemotherapy or radiation-related toxicities to grade =< 1, except for alopecia and peripheral neuropathy Performance status 0-2 Signed informed consent Exclusion Criteria: Prior treatment with eribulin Chemotherapy, radiation, or biological or targeted therapy within 3 weeks Hormonal therapy within 1 week Any investigational drug within 4 weeks Known brain metastases, unless previously treated and asymptomatic for 3 months and not progressive in size or number for 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eribulin mesylate<br>Eribulin mesylate 1.4 mg/m2 IV bolus over 2-5 minutes on days 1 and 8 every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: eribulin mesylate<br>* Given IV<br>* Other names: halichrondrin B analog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Product limits estimates of 6-month PFS will be computed using all patients enrolled on the study. 95% confidence intervals will be based on Greenwood standard errors. | From the first day of treatment to the first observation of disease progression or death due to any cause, assessed at 6 months | 
| Number of participants with serious adverse events (SAEs) | The rate of grade 3+ hematologic and non-hematologic toxicities will be computed for course 1 and for all courses combined. Safety evaluation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (BOR) | Exact 95% binomial confidence intervals will be computed for the BOR rate. BOR defined as the best response recorded from the start of treatment until disease progression/recurrence, evaluated according to RECIST 1.1. | Up to 2 years | 
| Overall survival (OS) |  | From first day of treatment to time of death due to any cause, assessed up to 2 years |