E7389 in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047034
First received: October 3, 2002
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: eribulin mesylate
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of E7389 (Halichondrin B Analog) (NSC# 707389) in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Pharmacokinetics of eribulin mesylate [ Time Frame: At baseline and at the first and third dose of treatment ] [ Designated as safety issue: No ]
    The pharmacokinetic data will be analyzed using compartmental and non-compartmental models for each patient.

  • In vivo anti-mitotic activity of E7389 by cell cycle analysis and immunohistochemistry [ Time Frame: At pre- and post-treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 31
Study Start Date: August 2002
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: eribulin mesylate
Given IV
Other Names:
  • B1939
  • E7389
  • ER-086526
  • halichrondrin B analog
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047034

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Morgan Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00047034     History of Changes
Other Study ID Numbers: NCI-2012-03076, PHI-39, U01CA062505, CDR0000257235
Study First Received: October 3, 2002
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014