Cancer: Solid Tumors
Conditions
Keywords
Cancer, solid tumors
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.
Interventions
DRUGE7080
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.
Sponsors
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerable Dose (MTD) of E7080 Repeatedly Administered Twice a Day | 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. |
| DLT of E7080 Repeatedly Administered Twice a Day | 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
| Measure | Time frame | Description |
|---|---|---|
| Determine the Clinical Dose for Phase II Study Based on Safety and Pharmacokinetic Profile | Every 3 weeks | — |
| To Elucidate the Pharmacokinetic Profile of E7080 | Every 3 weeks | — |
| To Make Exploratory Analyses of Pharmacodynamic Markers | Every 3 weeks | — |
| Evaluate the Anti-tumor Activity of E7080 | Every 3 weeks | — |
| Number of Participants With Adverse Events / Serious Adverse Events | Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. | Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E7080 Group 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. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | E7080 Group |
|---|---|
| Age, Continuous | 50.7 Years STANDARD_DEVIATION 11.1 |
| Sex/Gender, Customized Female | 17 Participants |
| Sex/Gender, Customized Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 7 / 27 |
Outcome results
Primary
DLT of E7080 Repeatedly Administered Twice a Day
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.
Time frame: up to 4 weeks
Population: Registered participants were included in the tolerability analysis set with the exception of the ineligible participants, participants with a treatment compliance rate of less than 75%, and participants who discontinued the study for reasons other than occurrence of DLT. However, cases of DLT shall be included in analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7080 Group | DLT of E7080 Repeatedly Administered Twice a Day | 1 Participants with DLT |
| E7080 - 20 mg Group | DLT of E7080 Repeatedly Administered Twice a Day | 2 Participants with DLT |
Primary
Maximum Tolerable Dose (MTD) of E7080 Repeatedly Administered Twice a Day
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.
Time frame: up to 4 weeks
Population: Registered participants were included in the tolerability analysis set with the exception of the ineligible participants, participants with a treatment compliance rate of less than 75%, and participants who discontinued the study for reasons other than occurrence of DLT. However, cases of DLT shall be included in analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7080 Group | Maximum Tolerable Dose (MTD) of E7080 Repeatedly Administered Twice a Day | 13 mg BID |
Secondary
Determine the Clinical Dose for Phase II Study Based on Safety and Pharmacokinetic Profile
Time frame: Every 3 weeks
Secondary
Evaluate the Anti-tumor Activity of E7080
Time frame: Every 3 weeks
Secondary
Number of Participants With Adverse Events / Serious Adverse Events
Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Time frame: Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons.
Population: All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7080 Group | Number of Participants With Adverse Events / Serious Adverse Events | 27 Participants |
Secondary
To Elucidate the Pharmacokinetic Profile of E7080
Time frame: Every 3 weeks
Secondary
To Make Exploratory Analyses of Pharmacodynamic Markers
Time frame: Every 3 weeks