cancer in the bladder neoplasia
Conditions
Interventions
None listed
Sponsors
Eisai
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria Patients may be entered in the study only if they meet all of the following criteria: 1. Male or female patient at least 18 years of age; 2. Histologically or cytologically confirmed, locally advanced Stage 4 (eg., T4b) or metastatic transitional cell cancer of the bladder, including other transitional cell cancers of the urothelium (prostate, urethra, ureter, and renal pelvis); 3. Not previously treated with systemic chemotherapy for metastatic bladder cancer (one regimen of adjuvant or neoadjuvant chemotherapy is permitted). Patients must have a disease-free interval of 6 months after adjuvant therapy; 4. At least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1) guidelines; 5. Life expectancy of *3 months; 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1; 7. Patients must have active bowel function defined as at least 3 bowel movements per week according to subject history and must be willing to maintain a diary of bowel function prior to dosing and continuing through completion of study treatment. Laxatives may be used to maintain adequate bowel function; 8. Patients must have adequate renal function as evidenced by calculated creatinine clearance *55 mL/min per the Cockcroft and Gault formula; 9. Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) *1.5 X 109/L, hemoglobin *10.0 g/dL (a hemoglobin
Exclusion criteria
Exclusion criteria: Exclusion Criteria Patients will not be entered in the study for any of the following reasons: 1. Prior treatment with epothilone, ixabepilone, patupilone, vinflunine, halichondrin B, and/or halichondrin B chemical derivatives; 2. History of other malignancies except: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated, a) in situ carcinoma of the uterine cervix, or b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively treated solid tumor with no evidence of disease for at least 3 years; 3. Presence of brain metastases, unless the patient has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization; 4. Received an investigational agent, chemotherapy, biological therapy, hormonal therapy, targeted therapy, or radiotherapy within 30 days prior to commencing study treatment, or have not recovered from all treatment-related toxicities to Common Toxicity Criteria (CTC) Grade less than or equal to 1, except for alopecia; 5. Are currently receiving an investigational agent or any other systemic anticancer treatment, including palliative radiotherapy; 6. Significant cardiovascular impairment (history of congestive heart failure New York Heart Association [NYHA] Grade >2, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia); 7. Subjects with a high probability of Long QT Syndrome; 8. Patients with organ allografts requiring immunosuppression; 9. Known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV); 10. Hypersensitivity to halichondrin B and/or halichondrin B chemical derivative; 11. Prior pelvic radiation; 12. History of known or suspected peritoneal carcinomatosis with risk of bleeding or perforation, or intraluminal or serosal metastatic lesions with risk of bleeding or perforation of any lesions; 13. History of abdominal adhesions, fistula, diverticulitis, gastrointestinal perforation, intra-abdominal abscess, documented peptic ulcer disease (active gastroesophageal reflux disease/dyspepsia are allowed), or other gastrointestinal conditions with increased risk of perforation; 14. Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v.4.0) Grade * 2 constipation; 15. CTCAE v.4.0 Grade *2 peripheral neuropathy; 16. Have any medical condition that would interfere with the conduct of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib The maximum tolerated dose (MTD) of eribulin administered in combination with gemcitabine and cisplatin will be determined as follows: If 2 dose limiting toxicities (DLTs) occur at any dose level, that dose will be defined as not tolerated and the MTD will either be defined as the preceding dose or an intermediate dose. To evaluate an intermediate dose, additional dosing cohorts may be added to more accurately define the MTD. Phase II Safety parameters will include: AEs; vital signs; ECOG PS; clinical laboratory evaluations; physical examinations; and 12 lead electrocardiograms (ECGs). All AE data will be collected at each visit using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Preliminary Efficacy: The primary exploratory efficacy endpoint will be the median progression-free survival (PFS) defined as the time from the date of randomization of a patient until the sooner of (1) the date of first documented progression of such patient*s disease based on Investigator assessments according to RECIST (version 1.1) or (2) the date of such patient*s death due to any cause. Auxiliary Efficacy: Secondary exploratory efficacy endpoints include proportion of PFS at Week 12, median time to progression (TTP), overall survival (OS), and objective response rate (ORR). Subgroup summaries will be carried out for the metastatic disease status strata (visceral metastases stratum, and non-visceral metastases stratum). | — |
Countries
Netherlands
Outcome results
None listed