An Open-Label, Multicenter, Randomized Phase Ib/II Study of 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

Completed

• Conditions: cancer in the bladder; neoplasia; 10038364; 10043413

• Registration Number: NL-OMON39526
• Lead Sponsor: Eisai

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 15

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 <10.0 g/dL at Screening is acceptable if it is corrected to *10 g/dL by growth factor or transfusion prior to first dose), and platelet count *100 X 109/L;
10. Patients must have adequate liver function as evidenced by bilirubin *1.5 times the upper limit of the normal range (ULN), and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) *3 X ULN (in the case of liver metastases, *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; and
14. Ability to understand and willingness to sign a written informed consent.

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified