Eribulin Mesylate and Cisplatin in Treating Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This trial is studying the side effects and best dose of eribulin mesylate and cisplatin in treating patients with advanced solid tumors.Drugs used in chemotherapy, such as eribulin mesylate and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Detailed Description
-----------------
Primary Objectives: I. To determine the maximum tolerated dose of E7389 and cisplatin in patients with advanced solid tumors. II. To determine the safety and toxicity of this regimen in these patients. III. To determine the pharmacokinetics of this regimen in these patients. Outline: This is a multicenter, dose-escalation study. Patients receive eribulin mesylate IV over 5 minutes on days 1, 8, and 15 and cisplatin IV over 30-60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for up to 8 weeks.

Official Title
-----------------
A Phase 1 Study of Halichondrin B Analog (E7389) in Combination With Cisplatin in Advanced Solid Tumors

Conditions
-----------------
Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: eribulin mesylate
* Drug: cisplatin
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed malignant solid tumor Advanced disease, meeting both of the following criteria: Metastatic or unresectable disease and standard curative or palliative measures do not exist or are no longer effective. No known active brain metastases Life expectancy > 3 months ECOG performance status 0-2 Bilirubin normal No uncontrolled intercurrent illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social situation that would limit study compliance. Negative pregnancy test Fertile patients must use effective contraception Recovered from prior therapy No prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C). No prior targeted therapy within the past 4 weeks No prior immunotherapy within the past 4 weeks No prior radiotherapy within the past 4 weeks. No more than 2 prior chemotherapy regimens for advanced solid tumors. No other concurrent investigational agents. Bisphosphonate therapy (e.g., pamidronate or zolendronate) is not considered investigational therapy. No concurrent antiretroviral therapy for HIV-positive patients. No other concurrent anticancer agents or therapies. Tumor has spread to other parts of the body or cannot be removed by surgery. More than 4 weeks since chemotherapy, biological therapy, or radiation therapy. No more than two previous chemotherapy regimens for advanced solid tumor. WBC >= 3,000/mm^3 Platelet count >= 100,000/mm^3 Creatinine clearance >= 60 mL/min Absolute neutrophil count >= 1,500/mm³ AST and ALT =< 2.5 times upper limit of normal No prior cumulative cisplatin dose > 300 mg/m^2 No preexisting neuropathy <= grade 2 Not pregnant or nursing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Patients receive eribulin mesylate IV over 5 minutes on days 1, 8, and 15 and cisplatin IV over 30-60 minutes on day 1. | Drug: eribulin mesylate<br>* Given IV<br>* Other names: halichrondrin B analog;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Other: laboratory biomarker analysis<br>* correlative study<br>Other: pharmacological study<br>* correlative study<br>* Other names: pharmacological studies;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose determined by dose-limiting toxicity graded according to the NCI CTCAE version 4.0 |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. | From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 8 weeks | 
| Time to failure | Summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. | Up to 8 weeks |