Advanced/metastatic hormone-refractory prostate cancer. MedDRA version: 8.1 Level: PT Classification code 10060862 Term: Prostate cancer
Conditions
Interventions
Product Name: BOLD
Product Code: E7389
Pharmaceutical Form: Solution for infusion
CAS Number: 441045-17-6
Current Sponsor code: E7389
Sponsors
Eisai Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Males with histologically proven adenocarcinoma of the prostate that has progressed (a minimum of three consecutive rises in PSA (with the last value = 4 ng/mL) taken at least one 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) 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 (six 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 mitoxanthrone and/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 ULN (upper limit of normal) 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. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 the 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 non-melanoma 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of E7389 in the treatment of patients with advanced/metastatic hormone-refractory prostate cancer with and without prior chemotherapy with a tubulin-binding agent such as docetaxel. ; Secondary Objective: The secondary objective is to evaluate the safety of E7389 when administered as a bolus infusion in the treatment of patients with advanced/metastatic hormone-refractory prostate cancer with and without prior chemotherapy with a tubulin-binding agent such as docetaxel. When possible, pharmacogenomic analysis will be carried out to explore the relationships between clinical response to E7389 and the expression of alpha- and beta-tubulin isotypes, tau, stathmin, and MAP4, (as well as to describe potential mutations in the corresponding genes in tumors). ; Primary end point(s): Primary efficacy endpoint The primary efficacy endpoint is PSA Response: post-therapy declines in PSA of =50% will be confirmed as per Bubley criteria. Declines of less than 50% and increases of no more than 25% will be reported as Stable Disease. Secondary efficacy endpoint The secondary efficacy endpoint is duration of PSA response. Tertiary efficacy endpoints • Tumor Related Symptom Assessments measured by a visual analog scale (VAS), analgesic consumption, ECOG performance status, and weight change. • Progression Free Survival: Progressive disease will be defined as either an increase in PSA of at least 25%, an increase of the absolute value of PSA by at least 5 ng/mL, an increase in measurable disease as per RECIST, or clinical progression. • Objective tumor response rates (CR, PR, SD and PD) in patients with measurable disease will be determined based on RECIST criteria. Safety e | — |
Countries
Hungary, Spain, United Kingdom
Outcome results
None listed