Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00004006

Trial Description

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Title

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

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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. experience benefit.

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Brief Summary in Scientific Language

This open-label, multicenter, randomized study will consist of 2 phases:

- Phase Ib: a safety run-in period with 3 ascending doses of eribulin;

- Phase II: a randomized 2-arm design. Phase Ib Patients will be recruited into cohorts,
with a minimum of 3 and a maximum of 6 patients per cohort. All patients will receive
the same dose of gemcitabine (1000 mg/m2 on Days 1 and 8 of a 21-day cycle) and
cisplatin (70 mg/m2 on Day 1) in combination with eribulin (administered on Days 1 and
8 of the cycle). All patients in a cohort will receive the same dose level of eribulin.

The dose level of eribulin will be escalated for additional cohorts unless greater than 2
dose limiting toxicities (DLTs) are reported at the lower dose level(s) prior to enrollment
of the next dose level. If one DLT occurs at any dose level, the cohort will be expanded to
include up to a maximum of 6 patients.

A Dose Escalation Committee will determine when no further dose escalation is appropriate
and whether the MTD will be defined as a preceding dose or an intermediate dose.

Phase II Patients will be randomized in a 1:1 ratio to receive either eribulin in
combination with gemcitabine plus cisplatin (Arm 1) or gemcitabine plus cisplatin alone (Arm
2). The eribulin dose will be 1.0 mg/m2 administered on Days 1 and 8 of each 21-day
treatment cycle, the recommended Phase II dose for eribulin when administered in combination
gemcitabine plus cisplatin, as determined in the Phase Ib portion of the study.

Allocation of patients will be stratified based on metastatic disease status (patients with
visceral metastases versus patients with non-visceral metastases). This stratified
randomization will be centrally allocated across all centers via an Interactive Voice
Activated Response System (IVRS).

For both the Phase Ib and Phase II portions, 1 cycle of therapy will last 21 days, with a
maximum number of 6 gemcitabine plus cisplatin cycles. Radiologic examinations including a
computed tomography (CT) scan of the chest, abdomen, and pelvis as appropriate (and CT or
magnetic resonance imaging [MRI] scan as appropriate), will be performed during Screening
and after every 6 weeks while on therapy. In the case of dose delays, scans should be
performed according to the original Cycle 1 Day 1 schedule (ie, scans should not be
delayed). Radiographic assessments should be repeated at withdrawal if the last assessment
was obtained >3 weeks from withdrawal of therapy. Patients will be followed until death
following completion of therapy. Scans will be required every 2 months until documentation
of PD or the start of a next line of therapy, whichever occurs first. In patients
experiencing PD, follow-up will be for survival only and radiographic scans are not required

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Organizational Data

  •   DRKS00004006
  •   2012/09/06
  •   2010/05/17
  •   no
  •   [---]*
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Secondary IDs

  •   2009-015915-42 
  •   NCT01126749  (ClinicalTrials.gov)
  •   E7389-702  (Eisai Inc.)
  •   2009-015915-42 
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Health Condition or Problem studied

  •   Bladder Cancer
  •   C67 -  Malignant neoplasm of bladder
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Interventions/Observational Groups

  •   Drug: gemcitabine plus cisplatin
  •   Drug: E7389 in combination with gemcitabine plus cisplatin
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   I-II
  •   [---]*
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Primary Outcome

- Safety parameters; time frame: [Time Frame: AEs and conmeds - until study termination; lab tests Day 1 and every 21 days until study termination; ECGs - Day 1 and 21 days after therapy ended; Safety parameters: adverse events (AEs); vital signs; ECOG PS; clinical laboratory evaluations; physical examinations; and 12 lead electrocardiograms (ECGs).

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Secondary Outcome

- Efficacy Measures; time frame: Until disease progression or death; Progression-free survival (PFS)l [Time Frame: Until disease progression or death]
Time to Progression(TTP): Time Frame: Until disease progression or Death]
Overall survival (OS); [Time Frame: until death]
Overall Response Rate (ORR), the number and percentage of patients with Complete Response (CR); Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD) [Time frame: Until completion of study or every 2 months during follow-up for 1 year]

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Countries of Recruitment

  •   United States
  •   Germany
  •   Netherlands
  •   Spain
  •   Ukraine
  •   United Kingdom
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Locations of Recruitment

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Recruitment

  •   [---]*
  •   2010/04/30
  •   95
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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 >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 109/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 109/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.

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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 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 >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.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Eisai Inc.
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    •   [---]*
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  • start of 1:1-Block address other
    • PharmaBio Development Inc.
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    •   [---]*
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   6
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.