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

NCT01126749 | Terminated Phase 1 Results

• 2 other identifiers: E7389-7022009-015915-42
• Study Type: interventional
• Target: 92
• Locations: 6 countries
• Sites: 42

Brief 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.

Conditions

Bladder Cancer

Keywords

Locally Advanced or Metastatic Bladder Cancer, including other transitional cell cancers of the urothelium (prostate, urethra, ureter, and renal pelvis)

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0

  DLTs were clinically significant adverse events within 21 days of treatment judged by investigator at least possibly related to treatment. This included greater than or equal to (\>=) Grade 3 (G3) peripheral neuropathy, \>=G3 nausea and vomiting despite optimal anti-emetic treatment, any other non-hematologic toxicity of \>=G3 (except alopecia, single abnormal laboratory values the Investigator judged unlikely related to study therapy, had no clinical correlate, and resolved within 7 days, and hypersensitivity reaction to any of the compounds), Grade 4 neutropenia lasting over 7 days, febrile neutropenia (defined as fever \>=38.5 degrees Celsius with absolute neutrophil count below 1.0\*10\^9 per liter, G3 thrombocytopenia with nontraumatic bleeding (without therapeutic systemic anticoagulation) requiring platelet transfusion, Grade 4 thrombocytopenia (with or without nontraumatic bleeding), any study drug-related death, any other toxicity the dose escalation committee believed to be DLT.

  Cycle 1 (Cycle length=21 days)

• Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  TEAE was defined as an adverse event that had an onset date, or a worsening in severity on or after the first dose of study drug up to the end of the study. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, examining bowel movements, regular measurement of vital signs, eastern cooperative oncology group-performance status and electrocardiogram parameter values. SAE was any untoward medical occurrence that at any dose: resulted in death; life threatening required inpatient hospitalization; resulted in persistent, significant disability; was congenital anomaly/birth defect or medically important due to other reasons than mentioned criteria. Number of participants with TEAEs and SAEs were reported.

  From the first dose of study drug up to approximately 6 years 3 months

Secondary Outcomes (5)

• Phase 2: Progression-free Survival (PFS)

  From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 6 years 3 months)

• Phase 2: Percentage of Participants With Overall Response

  From the date of randomization until CR or PR (Up to approximately 6 years 3 months)

• Phase 2: Percentage of Participants With Progression-free Survival at Week 12

  Week 12

• Phase 2: Time to Progression (TTP)

  From the date of randomization until the date of PD (Up to approximately 6 years 3 months)

• Phase 2: Overall Survival (OS)

  From the date of randomization until the date of death (Up to approximately 6 years 3 months)

Study Arms (2)

E7389 in combination with gemcitabine plus cisplatin

EXPERIMENTAL

Drug: Gemcitabine; Drug: E7389; Drug: Cisplatin

gemcitabine plus cisplatin

EXPERIMENTAL

Drug: Gemcitabine; Drug: Cisplatin

Interventions

Gemcitabine DRUG

Gemcitabine

E7389 in combination with gemcitabine plus cisplatin; gemcitabine plus cisplatin

E7389 DRUG

E7389

Also known as: Eribulin Mesylate

E7389 in combination with gemcitabine plus cisplatin

Cisplatin DRUG

Cisplatin

E7389 in combination with gemcitabine plus cisplatin; gemcitabine plus cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be entered in the study only if they meet all of the following criteria:
• Male or female patient greater than 18 years of age;
• 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)
• 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;
• At least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1) guidelines;
• Life expectancy of greater than or equal to 3 months;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1;
• 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;
• 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;
• 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;
• 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;
• 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;
• Females of childbearing potential must have a negative serum pregnancy test at screening;
• Females may not be breastfeeding;
• Ability to understand and willingness to sign a written informed consent.

You may not qualify if:

• Patients will not be entered in the study for any of the following reasons:
• Prior treatment with epothilone, ixabepilone, patupilone, vinflunine, halichondrin B, and/or halichondrin B chemical derivatives;
• 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;
• 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;
• 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;
• Are currently receiving an investigational agent or any other systemic anticancer treatment, including palliative radiotherapy;
• 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);
• Subjects with a high probability of Long QT Syndrome;
• Patients with organ allografts requiring immunosuppression;
• Known active infection with human immunodeficiency virus (HIV), hepatitis B, virus (HBV) or hepatitis C; virus (HCV);
• Hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
• Prior pelvic radiation;
• 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;
• 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;
• Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v.4.0) Grade greater than or equal to 2 constipation;

Sponsors & Collaborators

• Eisai Inc.: lead
• PharmaBio Development Inc.: collaborator

Study Sites (42)

Unknown Facility

Birmingham, Alabama, 35294, United States

Location

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Tucson, Arizona, 85715, United States

Location

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Fort Myers, Florida, 33916, United States

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St. Petersburg, Florida, 33705, United States

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Ann Arbor, Michigan, 48109, United States

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Las Vegas, Nevada, 89169, United States

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East Orange, New Jersey, 7018, United States

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Rochester, New York, 55904, United States

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Chattanooga, Tennessee, 37404, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77024, United States

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Webster, Texas, 77598, United States

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Huntington, Virginia, 25704, United States

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Northfork, West Virginia, 23502, United States

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Aachen Northwest, 52074, Germany

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Berlin, Germany

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Essen, Northwest, 45136, Germany

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Goch, Northwest, 47574, Germany

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Hamburg, HH, 20246, Germany

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Tuebingen, BW, 72076, Germany

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Wiesbaden, HE, 65191, Germany

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Maastricht, 6229, Netherlands

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Nieuwegein, 3435, Netherlands

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Nijmegen, 6525, Netherlands

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Barcelona, 8003, Spain

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Barcelona, 8025, Spain

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Elche- Alicante, 3203, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Madrid, 28050, Spain

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Sabadell, 8208, Spain

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Dnipropetrovsk, 49005, Ukraine

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Dnipropetrovsk, 49102, Ukraine

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Donetsk, 83092, Ukraine

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Kharkiv, 61037, Ukraine

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Kyiv, 3022, Ukraine

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Lviv, 79031, Ukraine

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Leicester, United Kingdom

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Liverpool, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Southampton, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Gemcitabine; eribulin; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

Due to the lack of a clear definition for PFS censoring rules and deviation from the statistical analysis plan relating to interim analyses, the PFS analysis was deemed unreliable and therefore data was not collected and reported.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2010
• First Posted: May 20, 2010
• Study Start: April 16, 2010
• Primary Completion: May 8, 2015
• Study Completion: July 20, 2016
• Last Updated: February 28, 2022
• Results First Posted: February 28, 2022

Record last verified: 2022-01

Locations

UA (6); GB (5); DE (7); NL (3); US (14); ES (7)