Evaluating E7389 in Patients With Hormone Refractory Prostate Cancer With Advanced and/or Metastatic Disease Stratified by Prior Chemotherapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00278993
First received: January 17, 2006
Last updated: April 16, 2012
Last verified: April 2012
  Purpose

This is a multi-centre, phase II, open-label, two-stage design, single-arm study in patients with hormone-refractory prostate cancer (HRPC) with advanced (rising PSA) and/or metastatic disease and who have had prior anti-androgen therapy. The study will further explore the efficacy of E7389 by enrollment of patients into two strata: those who have had no prior systemic chemotherapy for their disease (except for mitoxantrone and estramustine), and those who failed no more than one previous chemotherapeutic regimen with tubulin-binding agents such as docetaxel.


Condition Intervention Phase
Prostate Cancer
Drug: E7389
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Open Label, Two Stage Design Study Evaluating E7389 in Patients With Hormone Refractory Prostate Cancer With Advanced and/or Metastatic Disease Stratified by Prior Chemotherapy

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Objective Prostate Specific Antigen (PSA) Response Rate Based on Bubley Criteria [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Bubley Criteria: Patients must have progressive disease to enter study. For outcomes, PSA response must show at least 50% decrease. Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir. PSA progressive disease- 25% increase from baseline or increase of 5 ng/mL along with measureable disease Stable disease- decline of less than 50% and not more than 25% increase.


Secondary Outcome Measures:
  • Duration of Prostate Specific Antigen Response Based on Bubley Criteria [ Time Frame: 12 months. ] [ Designated as safety issue: No ]
    Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir.

  • Progression Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    From the date study treatment was initiated until the earliest date of the first PSA assessment that determined progressive disease, or the death of death if death occurred without disease progression.

  • Overall Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Best Objective Tumor Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Based on Response Evaluation Criteria in Solid Tumors (RECIST), consisting of complete response (CR) plus partial response (PR). Defined as the best response 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).


Enrollment: 108
Study Start Date: January 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
With stratification
Drug: E7389
Intravenous 1.4 mg/m2 on a 3-week course.

  Eligibility

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

Inclusion criteria:

  1. Males with histologically proven adenocarcinoma of the prostate that has progressed (ie. a minimum of 3 consecutive rises in Prostate Specific Antigen (PSA) (with the last value ≥ 4 ng/mL) taken at least 1 week apart prior to study entry) despite castration or maintenance of castrate-level testosterone (defined as serum testosterone ≤ .50 ng/dL or 1.7 nmol/L), or progressed during non-hormonal chemotherapy.

    Note: Patients previously treated with an antiandrogen must have disease progression documented after antiandrogen withdrawal. Those who have not undergone orchiectomy must continue medical castration with a gonadotropin-releasing hormone analog. At least 4 weeks must have elapsed between the withdrawal of antiandrogens (6 weeks in the case of nilutamide or bicalutamide and four weeks in the case of flutamide or other secondary hormonal therapy) and enrollment, so as to avoid the possibility of confounding results of the response due to antiandrogen withdrawal.

  2. Patients must fulfill one of the following two criteria to be stratified:

    • No prior chemotherapy (except mitoxantrone or estramustine) for advanced and/or metastatic disease as defined in inclusion criteria #1.
    • Failure of no more than one previous chemotherapeutic regimen with tubulin binding agents such as docetaxel.
  3. Resolution of all chemotherapy or radiation-related toxicities to less than grade 2 severity, except neuropathy and alopecia
  4. Age ≥ 18 years.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
  6. Life expectancy of ≥ 3 months.
  7. Adequate renal function as evidenced by serum creatinine ≤ 1.5 times upper limits of normal (ULN) or calculated creatinine clearance ≥ 40 mL/minute (min) per the Cockcroft and Gault formula.
  8. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, hemoglobin ≥ 9.0 g/dL (or 5.5 mmol/L), and platelet count ≥ 100 x 10^9/L. Adequate liver function as evidenced by bilirubin ≤ 1.5 x ULN, alanine transaminase (ALT), and aspartate transaminase (AST) ≤ 3 x ULN (in the case of liver metastases ≤ 5 x ULN).
  9. Patients willing and able to complete the VAS (Visual Analog Scale).
  10. Patients willing and able to comply with the study protocol for the duration of the study.
  11. 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:

  1. Patients who have received chemotherapy, radiation, or experimental therapy within 4 weeks of start of E7389 treatment
  2. Radiation therapy encompassing ≥30% of marrow or treatment with radioactive strontium
  3. Patients who require therapeutic anti-coagulant therapy with warfarin or related compounds; (mini dose warfarin or related compounds are permitted).
  4. Severe / uncontrolled intercurrent illness/infection.
  5. 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)
  6. Patients with organ allografts.
  7. Patients with known immunosuppression such as positive HIV status.
  8. Patients who have had a prior malignancy, other than nonmelanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ 5 years previously with no subsequent evidence of recurrence.
  9. Patients with pre-existing neuropathy > Grade 2
  10. Patients with brain or subdural metastases are not eligible, except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least two weeks before starting treatment with E7389.
  11. Patients with meningeal carcinomatosis.
  12. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
  13. Patients who participated in a prior E7389 clinical trial.
  14. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00278993

Locations
United States, Colorado
Dr. Robert Jotte
Denver, Colorado, United States, 80218
United States, Florida
Melbourne Internal Medicine Associates
Melbourne, Florida, United States, 32901
Ocala Oncology Center PL
Ocala, Florida, United States, 34474
United States, Indiana
Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46227
United States, Minnesota
Minnesota Hematology Oncology
Burnsville, Minnesota, United States, 33557
United States, Missouri
Missouri Cancer Associates
Columbia, Missouri, United States, 65201
United States, New York
New York Oncology Hematology, P.C.
Albany, New York, United States, 12208
St. Luke's Roosevelt Hospital Center
New York, New York, United States, 10019
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Raleigh Hematology Oncology Associates PL
Raleigh, North Carolina, United States, 27607
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
US Oncology
Dallas, Texas, United States, 75204
El Paso Cancer Treatment Center
El Paso, Texas, United States, 79915
Texas Oncology PA
Fort Worth, Texas, United States, 76104
Texas Oncology PA
Tyler, Texas, United States, 75702
Tyler Cancer Center
Tyler, Texas, United States, 75702
Deke Slayton Cancer Center
Webster, Texas, United States, 77598
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23505
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Asha Das Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00278993     History of Changes
Other Study ID Numbers: E7389-G000-204
Study First Received: January 17, 2006
Results First Received: December 22, 2011
Last Updated: April 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Prostate cancer
metastatic disease

Additional relevant MeSH terms:
Neoplasm Metastasis
Prostatic Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 16, 2014