Eribulin Mesylate and Cisplatin in Treating Patients With Advanced Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: cisplatin; Drug: eribulin mesylate; Other: pharmacological study; Other: laboratory biomarker analysis

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • University of Southern California/Norris Cancer Center
    • Sacramento, California, United States, 95817
      • University of California at Davis Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 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: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Drug: eribulin mesylate; Given IV; Other Names: E7389; ER-086526; B1939; halichrondrin B analog; Other: pharmacological study; correlative study; Other Names: pharmacological studies; Other: laboratory biomarker analysis; correlative study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marianna Koczywas, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 20, 2006
• First Submitted That Met QC Criteria: December 20, 2006
• First Posted (Estimate): December 22, 2006

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 19, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: NCI-2009-00168 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA033572 (U.S. NIH Grant/Contract); U01CA062505 (U.S. NIH Grant/Contract); PHI-55 (Other Identifier: City of Hope Medical Center); CDR0000518290; 7427 (Other Identifier: CTEP)