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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00278993
• Other study ID #: E7389-G000-204
• Secondary ID: 2005-004271-37
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2006
• Last updated: June 30, 2014
• Start date: January 2006
• Est. completion date: January 2008

Study information

• Verified date: April 2012
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Neoplasms, Second Primary
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• E7389
Intravenous 1.4 mg/m2 on a 3-week course.

Locations

Country	Name	City	State
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Minnesota Hematology Oncology	Burnsville	Minnesota
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	US Oncology	Dallas	Texas
United States	Dr. Robert Jotte	Denver	Colorado
United States	El Paso Cancer Treatment Center	El Paso	Texas
United States	Texas Oncology PA	Fort Worth	Texas
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Columbia University Medical Center	New York	New York
United States	St. Luke's Roosevelt Hospital Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Ocala Oncology Center PL	Ocala	Florida
United States	Raleigh Hematology Oncology Associates PL	Raleigh	North Carolina
United States	Texas Oncology PA	Tyler	Texas
United States	Tyler Cancer Center	Tyler	Texas
United States	Deke Slayton Cancer Center	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Prostate Specific Antigen (PSA) Response Rate Based on Bubley Criteria	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.	12 months	No
Secondary	Duration of Prostate Specific Antigen Response Based on Bubley Criteria	Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir.	12 months.	No
Secondary	Progression Free Survival	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.	12 months	No
Secondary	Overall Survival		12 months	No
Secondary	Best Objective Tumor Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	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).	12 months	No