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Bladder CancerPhase 1/2NCT01126749

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

A Phase 1/2 study testing Gemcitabine, E7389 and Cisplatin in people with Bladder Cancer, run by Eisai Inc. at 42 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Gemcitabine, E7389 and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
42 sitesin 6 countries
Study dates
16 Apr 2010to 20 Jul 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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;
  • CTCAE v.4.0 Grade greater than or equal to 2 peripheral neuropathy;
  • Have any medical condition that would interfere with the conduct of the study.

Trial locations and contacts

42 sites in 6 countries.

42 sites in 6 countries

United States14 sites

  • Study site

    Ann Arbor, Michigan, 48109

  • Study site

    Birmingham, Alabama, 35294

  • Study site

    Chattanooga, Tennessee, 37404

  • Study site

    East Orange, New Jersey, 7018

  • Study site

    Fort Myers, Florida, 33916

  • Study site

    Fort Worth, Texas, 76104

  • Study site

    Houston, Texas, 77024

  • Study site

    Huntington, Virginia, 25704

  • Study site

    Las Vegas, Nevada, 89169

  • Study site

    Northfork, West Virginia, 23502

  • Study site

    Rochester, New York, 55904

  • Study site

    St. Petersburg, Florida, 33705

  • Study site

    Tucson, Arizona, 85715

  • Study site

    Webster, Texas, 77598

Other trials in United States

Germany7 sites

  • Study site

    Aachen Northwest, 52074

  • Study site

    Berlin

  • Study site

    Essen, Northwest, 45136

  • Study site

    Goch, Northwest, 47574

  • Study site

    Hamburg, HH, 20246

  • Study site

    Tuebingen, BW, 72076

  • Study site

    Wiesbaden, HE, 65191

Other trials in Germany

Spain7 sites

  • Study site

    Barcelona, 8003

  • Study site

    Barcelona, 8025

  • Study site

    Elche- Alicante, 3203

  • Study site

    Madrid, 28034

  • Study site

    Madrid, 28040

  • Study site

    Madrid, 28050

  • Study site

    Sabadell, 8208

Other trials in Spain

Ukraine6 sites

  • Study site

    Dnipropetrovsk, 49005

  • Study site

    Dnipropetrovsk, 49102

  • Study site

    Donetsk, 83092

  • Study site

    Kharkiv, 61037

  • Study site

    Kyiv, 3022

  • Study site

    Lviv, 79031

Other trials in Ukraine

United Kingdom5 sites

  • Study site

    Leicester

  • Study site

    Liverpool

  • Study site

    London

  • Study site

    Manchester

  • Study site

    Southampton

Other trials in United Kingdom

Netherlands3 sites

  • Study site

    Maastricht, 6229

  • Study site

    Nieuwegein, 3435

  • Study site

    Nijmegen, 6525

Other trials in Netherlands

About this study

Official 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

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.

Read the detailed description

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 greater than 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.

Conditions
Bladder Cancer
Being tested
Gemcitabine, E7389, Cisplatin
Keywords
Locally Advanced or Metastatic Bladder Cancer, including other transitional cell cancers of the urothelium (prostate, urethra, ureter, and renal pelvis)
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01126749
Study groupRoleWhat they receive
E7389 in combination with gemcitabine plus cisplatinExperimentalNot described
Receives: Drug: Gemcitabine; Drug: E7389; Drug: Cisplatin
gemcitabine plus cisplatinExperimentalNot described
Receives: Drug: Gemcitabine; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (Cycle length=21 days)

  2. 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.

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

Secondary outcomes (5)

  1. Phase 2: Progression-free Survival (PFS)

    PFS was defined as the time from the date of randomization until the earlier of the following two events: the date of disease progression (PD) or the date of death based on response evaluation criteria in solid tumor (RECIST) version (v) 1.1. PD was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

    Measured: 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)

  2. Phase 2: Percentage of Participants With Overall Response

    Overall response rate was defined as the percentage of participants with the best confirmed response of complete response (CR) or partial response (PR) based on RECIST v1.1. CR was defined as complete disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline summed longest diameters.

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

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

    PFS was defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on RECIST v1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

    Measured: Week 12

  4. Phase 2: Time to Progression (TTP)

    TTP was defined as the time from the date of randomization until the date of PD based on RECIST v1.1. PD was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking in reference the smallest summed longest diameters on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression.

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

  5. Phase 2: Overall Survival (OS)

    OS was defined as the time from the date of randomization until the date of death due to any cause.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2010 (estimated)
  2. Study start16 Apr 2010
  3. Primary completion8 May 2015
  4. Study completion20 Jul 2016

Why it stopped: Study was terminated as per sponsor's decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01126749
Sponsor's protocol ID
E7389-702
Other IDs
2009-015915-42, 2009
Status last verified
Jan 2022
First submitted
17 May 2010
Last updated
28 Feb 2022
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Gemcitabine, E7389 and Cisplatin in people with Bladder Cancer, run by Eisai Inc. at 42 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States, Germany, Spain, Ukraine, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Cycle 1 (Cycle length=21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01126749.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.

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