A Study of E7389 in Advanced/Metastatic Breast Cancer Patients

This study has been completed.
Sponsor:
Information provided by:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00097721
First received: November 29, 2004
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to determine if E7389 is a safe and effective treatment for advanced/metastatic breast cancer.


Condition Intervention Phase
Breast Neoplasms
Drug: E7389
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Open Label Study of E7389 (Halichondrin B Analog) in Patients With Advanced/Metastatic Breast Cancer Previously Treated With Chemotherapy Including An Anthracycline and A Taxane

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Overall Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Confirmed 4 to 8 weeks after first observed ] [ Designated as safety issue: No ]
    Defined as the percentage of subjects with CR or PR from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: From CR or partial response PR (whichever recorded first) to date of recurrent or progressive disease ] [ Designated as safety issue: No ]
    Measured from the time measurement criteria were met for complete response (CR) or partial response (PR) (whichever was first recorded) until the first date that recurrent progressive disease was objectively documented (taking as a reference for progressive disease the smallest measurements recorded since the treatment started).

  • Progression Free Survival [ Time Frame: From start of study drug administration to progressive disease or death ] [ Designated as safety issue: No ]
    Defined as the time from start of study drug administration until progressive disease or death from any cause during the study period in the absence of disease progression.

  • Overall Survival [ Time Frame: From start of study drug administration to death ] [ Designated as safety issue: No ]
    Defined as the time from the start of study drug administration until death from any cause

  • Change From Baseline to Study Termination in Quality of Life Measures Using Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores [ Time Frame: At Screening, Day 1 of each cycle, and 30 days after last dose of study drug ] [ Designated as safety issue: No ]
    The FACT-B questionnaire consists of 36 questions each scored from 0-4. The total score is calculated by summing these scores. The total possible range is from 0 to 144. The higher scores indicate a better health-related quality of life. This measures emotional, functional, physical, and social well being as well as concerns specific to patients with breast cancer.


Enrollment: 104
Study Start Date: September 2004
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E7389 Drug: E7389
The first cohort of subjects were to receive E7389 1.4 mg/m^2 as an intravenous (IV) bolus on Days 1, 8, and 15 of a 28-day cycle. A second cohort of subjects was added and were to receive E7389 1.4 mg/m^2 as an IV bolus on Days 1 and 8 of a 21-day cycle.

Detailed Description:

The primary objective is to determine the response rate (RR) to E7389 monotherapy administered as an IV bolus of 1.4 mg/m^2 on Days 1, 8, and 15 of a 28-Day cycle and on Days 1 and 8 of a 21-day cycle in patients with advanced/metastatic breast cancer treated with chemotherapy including an anthracycline and a taxane, with previously documented progression during or within six months following the last dose of prior chemotherapy.

The secondary objectives are to evaluate:

  • The safety and tolerability of E7389 monotherapy in this patient population;
  • The antitumor activity of E7389 as determined by duration of response, time to progression, and overall survival;
  • Quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire/tumor-related symptom improvement or worsening measured by pain intensity on a visual analog scale (VAS), analgesics consumption, weight changes and performance status (PS);
  • Tumor pharmacogenetics and their possible relationship to response (assessment of beta-tubulin isotype mRNA on biopsy sample) in patients who have signed a separate consent form
  Eligibility

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

Inclusion Criteria:

  • Female patients with histologically or cytologically confirmed carcinoma of the breast
  • Patients with advanced/metastatic disease that is not amenable to curative therapy (either surgery or radiation therapy)
  • Patients must have measurable disease by the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one diameter (at least 10 mm in longest diameter (LD) by spiral computer tomography (CT) scan, or at least 20 mm by standard techniques; If the only measurable lesion is a lymph node, it must measure at least 20 mm in LD. If a single lesion is identified as the target lesion, a cytological or histological confirmation of breast carcinoma is required.
  • Patients must have had prior treatment with an anthracycline and a taxane (either sequential or in combination) and may have had prior treatment with other agents as well.
  • Patients must have progressed within six months of the last dose of chemotherapy, or experienced disease progression while receiving chemotherapy for advanced/metastatic disease.
  • Resolution of all chemotherapy or radiation-related toxicities to less than grade 1 severity
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (APPENDIX 4) of 0 or 1
  • Life expectancy of ≥ 3 months
  • Adequate renal function as evidenced by serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/minute (min) per the Cockcroft and Gault formula
  • Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin <10.0 g/dL would be acceptable if it can be corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/L
  • Adequate liver function as evidenced by bilirubin ≤ 1.5 mg/dL and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) ≤ 3 times the upper limits of normal (ULN) (in the case of liver metastases ≤ 5 x ULN)
  • Patients willing and able to complete the FACT-B questionnaire, Analgesic Diary, Pain VAS, and the tumor-related symptomatic assessment
  • Patients willing and able to comply with the study protocol for the duration of the study
  • A sample from the diagnostic biopsy (paraffin block) must be available
  • Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice

Exclusion Criteria:

  • Patients who have received chemotherapy, radiation, hormonal therapy, or Herceptin within 2 weeks of E7389 treatment start
  • Radiation therapy encompassing > 10% of marrow
  • Failure to recover from any chemotherapy related or other therapy related toxicity at study entry that is deemed to be clinically significant by the study investigator
  • Prior treatment with Mitomycin C or nitrosoureas
  • Prior high dose chemotherapy with hematopoietic stem cell rescue in the past two years
  • Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
  • Active symptomatic brain metastasis; Patients with central Nervous System (CNS) metastasis are considered eligible if they have completed local therapy and discontinued from corticosteroids for at least two weeks before starting treatment with E7389
  • Patients with meningeal carcinomatosis
  • Patients who require therapeutic anti-coagulant therapy with Warfarin or related compounds; Mini dose warfarin for catheter related thrombosis prophylaxis is permitted
  • Women who are pregnant or breast-feeding; Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Severe /uncontrolled intercurrent illness/infection
  • Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia)
  • Patients with organ allografts
  • Patients with known positive HIV status
  • Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ 5 years previously with no subsequent evidence of recurrence
  • Patients with pre-existing neuropathy > Grade 1
  • Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
  • Patients who participated in a prior E7389 clinical trial
  • Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from 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: NCT00097721

Locations
United States, Arkansas
Jonesboro, Arkansas, United States
United States, California
Deer Park, California, United States
La Verne, California, United States
Pasadena, California, United States
Pomona, California, United States
United States, Florida
Brooksville, Florida, United States
New Port Richey, Florida, United States
Plantation, Florida, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Mississippi
Southaven, Mississippi, United States
United States, Montana
Missoula, Montana, United States
United States, New York
Syracuse, New York, United States
United States, Ohio
Middletown, Ohio, United States
United States, Tennessee
Memphis, Tennessee, United States
United States, Texas
Amarillo, Texas, United States
Richardson, Texas, United States
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Dale Shuster, Ph.D. Eisai Inc.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00097721     History of Changes
Other Study ID Numbers: E7389-A001-201
Study First Received: November 29, 2004
Results First Received: January 9, 2012
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
breast neoplasm
breast cancer
breast tumor

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 24, 2014