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An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00280397
Recruitment Status : Completed
First Posted : January 23, 2006
Results First Posted : March 6, 2015
Last Update Posted : October 7, 2016
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The purpose of this study is to determine the maximum tolerable dose (MTD) and the related effects of E7080 administered to patients with solid tumors that are resistant to approved existing anti-tumor therapies, or for which no appropriate treatment is available.

Condition or disease Intervention/treatment Phase
Cancer: Solid Tumors Drug: E7080 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors
Study Start Date : January 2006
Actual Primary Completion Date : September 2008
Actual Study Completion Date : November 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Lenvatinib

Arm Intervention/treatment
Experimental: 1 Drug: E7080
E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.

Primary Outcome Measures :
  1. Maximum Tolerable Dose (MTD) of E7080 Repeatedly Administered Twice a Day [ Time Frame: up to 4 weeks ]
    The MTD was defined as the highest dose at which no dose limiting toxicity (DLT) was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.

  2. DLT of E7080 Repeatedly Administered Twice a Day [ Time Frame: up to 4 weeks ]
    DLTs were defined as grade 3 or more platelet count decrease, grade 4 neutropenia, any grade 3 or more nonhematologic toxicity (with exceptions of grade 4 hypertension not controlled by any antihypertensive drugs and grade greater than or equal to 3 vomiting and diarrhea not controlled by antiemetic or antidiarrheal drugs), and failure to administer more than 75% of the planned doses of E7080 during the same cycle due to toxicity.

Secondary Outcome Measures :
  1. To Elucidate the Pharmacokinetic Profile of E7080 [ Time Frame: Every 3 weeks ]
  2. Number of Participants With Adverse Events / Serious Adverse Events [ Time Frame: Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. ]
    Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.

  3. Determine the Clinical Dose for Phase II Study Based on Safety and Pharmacokinetic Profile [ Time Frame: Every 3 weeks ]
  4. Evaluate the Anti-tumor Activity of E7080 [ Time Frame: Every 3 weeks ]
  5. To Make Exploratory Analyses of Pharmacodynamic Markers [ Time Frame: Every 3 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Patients who have histologically and/or cytologically confirmed solid tumors requiring treatment.
  2. Patients with solid tumors which are resistant to approved conventional anti-tumor therapies, or for which no appropriate treatment is available.
  3. Patients who had completed all previous treatments (including surgery and radiotherapy) and supportive care (such as transfusion of blood, blood components and granulocyte colony-stimulating factor [G-CSF] treatment) at least 4 weeks before registration, and no sign or symptom of acute toxicity occurred in previous treatments.
  4. Patients 20 years or older and less than 75 years of age at the time of registration.
  5. Patients with 0 or 1 Performance Status (PS) established by Eastern Cooperative Oncology Group (ECOG.)
  6. Patients who can stay in hospital for more than 1 cycle of treatment.
  7. Patients who are expected to survive for more than 3 months from the start of study drug administration.
  8. Patients who have provided written informed consent for the participation in the study.

Exclusion criteria:

  1. Patients with clinical symptoms due to brain metastases requiring treatment.
  2. Patients who have any of the following laboratory test findings:

    1. Hemoglobin less than 9.0 g/dL
    2. Neutrophil count less than 1.5 x 10 9/L
    3. Platelet count less than 100 x 10 9/L
    4. Serum bilirubin greater than 1.5 mg/dL
    5. AST, ALT greater than 100 IU/L
    6. Serum creatinine greater than 1.5 mg/dL or creatinine clearance less than 50 mL/minute
  3. Patients with positive reaction for human immunodeficiency virus (HIV) or hepatitis virus C (HCV) antibody or hepatitis B virus surface (HBs) antigen, or patients with untreated serious infections.
  4. Patients with clinically significant cardiac disorders or unstable ischemic heart diseases including myocardial infarction within six months before the registration for the study.
  5. Patients with marked Baseline prolongation of QT/QTc interval (QTc interval greater than 450 msec for males or greater than 470 msec for females) using the Fridericia method for QTc analysis.
  6. Patients with hemorrhagic or thrombotic diseases or who are using therapeutic doses of anticoagulants such as aspirin, warfarin, or ticlopidine.
  7. Patients who are diagnosed with hypertension (defined as repeatedly measured blood pressure = 160/90 mmHg) at Screening, irrespective of use of antihypertensive drugs.
  8. Patients who have proteinuria greater than 1 on bedside testing.
  9. Patients who have history of insufficient gastrointestinal absorption, or patients who received gastric or intestinal anastomoses within 4 weeks before registration.
  10. Patients who have history of alcoholism, drug addiction or mental or physical disorders, which, in the investigators opinion, may impair study compliance.
  11. Patients who received any investigational drug within 30 days before the registration of the study.
  12. Patients who received CYP3A4 inhibitors including itraconazole, erythromycin, clarithromycin, diltiazem or verapamil during screening and who have to use these drugs during the study.
  13. Pregnant or nursing patients (all female patients with pregnancy potential must have negative pregnancy test performed before registration, and post-menopausal women must be amenorrheic for at least 12 months.) Female patients must use appropriate contraception.
  14. Fertile male patients who refuse to use contraception, or whose female partners are not using appropriate contraception.
  15. Patients who are judged by the investigator to be inappropriate for the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00280397

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Tokyo, Japan, 104-0045
Sponsors and Collaborators
Eisai Inc.
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Study Director: Akihiko Tsuruoka Eisai Co., Ltd.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Eisai Inc. Identifier: NCT00280397    
Other Study ID Numbers: E7080-J081-103
First Posted: January 23, 2006    Key Record Dates
Results First Posted: March 6, 2015
Last Update Posted: October 7, 2016
Last Verified: August 2016
Keywords provided by Eisai Inc.:
Cancer, solid tumors
Additional relevant MeSH terms:
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Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action