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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00280397
First received: January 20, 2006
Last updated: March 16, 2015
Last verified: October 2014

January 20, 2006
March 16, 2015
January 2006
September 2008   (final data collection date for primary outcome measure)
  • Maximum Tolerable Dose (MTD) of E7080 Repeatedly Administered Twice a Day [ Time Frame: up to 4 weeks ] [ Designated as safety issue: No ]
    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.
  • DLT of E7080 Repeatedly Administered Twice a Day [ Time Frame: up to 4 weeks ] [ Designated as safety issue: Yes ]
    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.
To determine the maximum tolerable dose (MTD) and the dose-limiting toxicities (DLT) of E7080 repeatedly administered twice a day.
Complete list of historical versions of study NCT00280397 on ClinicalTrials.gov Archive Site
  • To Elucidate the Pharmacokinetic Profile of E7080 [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events / Serious Adverse Events [ Time Frame: Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. ] [ Designated as safety issue: Yes ]
    Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
  • Determine the Clinical Dose for Phase II Study Based on Safety and Pharmacokinetic Profile [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]
  • Evaluate the Anti-tumor Activity of E7080 [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]
  • To Make Exploratory Analyses of Pharmacodynamic Markers [ Time Frame: Every 3 weeks ] [ Designated as safety issue: No ]
  • 1) To elucidate the pharmacokinetic profile of E7080
  • 2) To evaluate the safety and tolerability of E7080
  • 3) To determine the clinical dose for Phase II study based on safety and pharmacokinetic profile
  • 4) To evaluate the anti-tumor activity of E7080
  • 5) To make exploratory analysis of pharmacodynamic marker
Not Provided
Not Provided
 
An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors
An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Cancer: Solid Tumors
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.
Experimental: 1
Intervention: Drug: E7080

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
November 2008
September 2008   (final data collection date for primary outcome measure)

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.
Both
20 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00280397
E7080-J081-103
Not Provided
Eisai Inc.
Eisai Inc.
Not Provided
Study Director: Akihiko Tsuruoka Eisai Co., Ltd.
Eisai Inc.
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP