Eribulin Mesylate Administered in Combination With Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Alone as First-Line Therapy for Locally Advanced or Metastatic Bladder Cancer

• Status: Completed
• Trial end date: 2016-07-20
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether Patients with Locally Advanced or Metastatic Bladder Cancer who receive Eribulin Mesylate Administered in Combination with Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin Alone as First-Line Therapy is safety and tolerable when administered to patients with locally advanced or metastatic bladder cancer and to gain preliminary data on whether patients may benefit from this combination.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eisai Inc.
• Collaborator: PharmaBio Development Inc.
• Treatments: Cisplatin; Gemcitabine

Criteria

Inclusion Criteria

Patients may be entered in the study only if they meet all of the following criteria:

1. Male or female patient greater than 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 greater than or equal to 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 greater than or equal to 55 mL/min per the Cockcroft and Gault formula;

9. Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L, hemoglobin greater than or equal to 10.0 g/dL (a hemoglobin less than 10.0 g/dL at Screening is acceptable if it is corrected to greater than or equal to 10.0 g/dL by growth factor or transfusion prior to first dose), and platelet count greater than or equal to 100 x 10^9/L;

10. Patients must have adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limit of the normal range (ULN), and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases, less than or equal to 5 x ULN). If there are bone metastases, liver-specific alkaline phosphatase may be separated from the total and used to assess liver function instead of total alkaline phosphatase;

11. Male or female patients of child-producing potential must agree to use double barrier contraception, oral contraceptives, or avoidance of pregnancy measures during the study and for 90 days after the last day of treatment;

12. Females of childbearing potential must have a negative serum pregnancy test at screening;

13. Females may not be breastfeeding;

14. Ability to understand and willingness to sign a written informed consent.

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 greater than or equal to 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 greater than 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 greater than or equal to 2 constipation;

15. CTCAE v.4.0 Grade greater than or equal to 2 peripheral neuropathy;

16. Have any medical condition that would interfere with the conduct of the study.