E7389 in Treating Patients With Advanced Solid Tumors

Phase I Trial of E7389 (Halichondrin B Analog) (NSC# 707389) in Patients With Advanced Solid Tumors

Phase I trial to study the effectiveness of E7389 in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

Study Overview

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

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of E7389 administered as an IV bolus over 1-2 minutes weekly for 3 weeks.

II. To describe the toxicities of E7389. III. To evaluate the pharmacokinetics of E7389. IV. To determine the in vivo anti-mitotic activity of E7389 by cell cycle analysis and immunohistochemistry in pre- and post-treatment tumor biopsies.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive E7389 IV over 1-2 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for at least 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of E7389 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope

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:

• Advanced, histologically-confirmed solid tumors refractory to standard therapy or for which no standard therapy exists
• Karnofsky performance status of at least 60% and estimated survival of at least two months
• Serum creatinine =< 1.5 mg/dl or creatinine clearance >= 60 ml/min
• ANC >= 1,500/ul
• Platelets >= 100,000/ul
• Bilirubin =< 1.5 mg/dl
• SGOT and SGPT =< 2.5 times the upper limits of normal
• Prior to entry on study, a patient must be at least four weeks from prior chemotherapy (six weeks from nitrosoureas, 8 weeks from UCN-01) and have recovered from all side effects of prior therapy; there is no limit on the number of prior chemotherapy regimens
• Written, voluntary, informed consent of the patient must be obtained in compliance with institutional, state and federal guidelines
• Patients with brain metastases are INELIGIBLE for this study
• Due to concerns regarding possible drug interactions, patients with HIV taking anti-retroviral medications are INELIGIBLE
• Pregnant patients and patients who are breast feeding are INELIGIBLE; all patients of child-bearing potential, both male and female, must be advised to practice adequate contraception; premenopausal women must have a negative pregnancy test prior to entry on this study
• Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it inappropriate to treat the patient on this protocol are INELIGIBLE
• Patients currently being treated for a severe infection or who are recovering from major surgery are INELIGIBLE until recovery is deemed complete by the investigators
• All patients must have evaluable disease; the presence of measurable disease is NOT required for this phase I study; if unidimensionally measurable disease is present, baseline measurements of up to 3 indicator lesions should be made no earlier than four weeks prior to the first cycle of chemotherapy; pleural effusions, ascites and bone metastases are not considered measurable
• CBC, differential count, platelet count, and blood chemistries should be done no earlier than 72 hours prior to each cycle of chemotherapy
• Except for 4 weeks for tumor measurements and 72 hours for specified blood work, pretreatment tests should be done no earlier than two weeks prior to the first cycle of chemotherapy
• Once the MTD has been established, an additional10 patients will be accrued to obtain pre- and post-treatment biopsy material in order to validate the molecular targets of E7389 in man; therefore, to maximize likelihood of obtaining tissue from patients treated in the expanded MTD cohort, only patients with tumors appropriate for repeated biopsy are eligible during this stage of the study

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: Treatment (eribulin mesylate); Patients receive E7389 IV over 1-2 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for at least 4 courses in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: eribulin mesylate; Given IV; Other Names: E7389; ER-086526; B1939; halichrondrin B analog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD of eribulin mesylate defined as the highest dose tested in which no more than 1 of first 6 patients evaluated for toxicity experience dose-limiting toxicity (DLT) as assessed by NCI CTC version 2.0	Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, time of onset (i.e., course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by cycle.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of eribulin mesylate	The pharmacokinetic data will be analyzed using compartmental and non-compartmental models for each patient.	At baseline and at the first and third dose of treatment
In vivo anti-mitotic activity of E7389 by cell cycle analysis and immunohistochemistry		At pre- and post-treatment

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: October 3, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 7, 2013
• Last Update Submitted That Met QC Criteria: January 4, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NCI-2012-03076; U01CA062505 (U.S. NIH Grant/Contract); PHI-39; CDR0000257235 (Registry Identifier: PDQ (Physician Data Query))