Cancer
Conditions
Keywords
Cancer, Tumors, Phase I, E7389
Brief summary
The primary objective of this study is to determine the dose limiting toxicity and maximum tolerated dose of E7389 in patients with solid tumors. The secondary objectives are to investigate the pharmacokinetics, safety, estimated recommended dose, and anti-tumor effects (in evaluable cases) of E7389 in patients with solid tumors.
Interventions
DRUGE7389
E7389 will be administered intravenously on Days 1 and 8 of a 21 day cycle. The initial dose level will be 0.7 mg/m2, with planned dose levels of 1.0, 1.4, 2.0 mg/m2.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically or cytologically confirmed solid tumors. 2. Patients who have progressed on or following standard therapy and with no other treatment options. 3. Patients aged 20-74 when they give informed consent. 4. Patients having a performance status (PS) of Eastern Cooperative Oncology Group (ECOG) 0 or 1. 5. Patients who can stay at the hospital from the start of the study drug treatment to 2 weeks of the first cycle. 6. Patients having adequate function of major organs (bone marrow, liver, kidney and lungs): (1) Neutrophil count 1,500/mm3 (2) Platelet count 100,000/mm3 (3) Hemoglobin 9.0 g/dL (4) Aspartate aminotransferase \[AST\] 2.5 times the upper limits of normal (ULN) in institute, unless related to liver involvement by tumor, in which case 5.0 times ULN (5) Alanine aminotransferase \[ALT\] 2.5 times ULN in institute, unless related to liver involvement by tumor, in which case 5.0 times ULN (6) Total bilirubin 1.5 times ULN in institute (7) Serum creatinine 1.5 times ULN in institute (8) Pulse oximeter oxygen saturation 90% 7\. Patients with no adverse drug reactions (excluding alopecia, etc.) that were caused by the prior therapy or could influence the safety evaluation of the study drug. The withdrawal periods required from the completion of the prior therapy to the start of the study drug therapy are as follows: 1. Chemotherapy (excluding oral 5-FU and molecular target drugs), surgical therapy, other study drugs: 4 weeks 2. Nitrosourea agents, mitomycin C: 6 weeks 3. Radiotherapy, endocrinotherapy, immunotherapy, oral 5-FU, molecular target drugs, blood transfusion, blood products, G-CSF and other hematopoietic factors: 2 weeks 8\. Patients who give written informed consent. 9\. Patients with an expected survival of longer than 3 months from the start of the study drug therapy.
Exclusion criteria
1. Patients with systemic infection with a fever (38°C). 2. Patients with a large amount of pleural effusion, ascites and pericardial fluid requiring drainage. 3. Patients with brain metastasis with clinical symptoms. 4. Patients with serious complications: (1) Patients with uncontrollable cardiac disease such as ischemic heart disease and arrhythmia at a level of severity that needs to be treated (excluding left ventricular hypertrophy, mild left ventricular volume overload and mild right leg block that accompany hypertension) (2) Patients with myocardial infarction within 6 months prior to study entry (3) Patients with a complication of hepatic cirrhosis (4) Patients with interstitial pneumonia and pulmonary fibrosis (5) Patients with a bleeding tendency 5. Women who are pregnant or breastfeeding, or premenopausal women of childbearing potential. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Premenopausal women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test, or have not agreed to use adequate measures of contraception. 6. Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception. 7. Patients who have tested positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or hepatitis B virus surface antigen (HBsAg). 8. Patients who need continuous systemic steroid therapy during the study period. 9. Patients who need continuous use of phenytoin, carbamazepine, rifampicin and/or barbiturate which induces cytochrome P450 (CYP3A4), a drug-metabolizing enzyme, during the study period. 10. Patients who have received extensive radiation therapy (30% or more of bone marrow). 11. Patients who refused to receive a supportive therapy of blood transfusion by suppressing bone marrow. 12. Patients who are participating in other clinical studies. 13. Patients whom the investigator or subinvestigator has judged inappropriate for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 3 Weeks | MTD was the lowest dose at which a dose limiting toxicity occurred. |
| Number of Subjects Who Experienced Dose Limiting Toxicity (DLT) | 3 weeks | DLT is an adverse drug reaction defined as 1)Grade 4 neutropenia for 5 days, 2)\>/=Grade 3 febrile neutropenia, 3)\>/=Grade 3 neutropenia requiring iv antibiotics, 4)Grade 4 thrombocytopenia, 5)\>/=Grade 3 nonhematologic toxicity, 6)Omission of study drug on Day 8 due to \>/=Grade 3 neutropenia or thrombocytopenia or investigator decision. |
Secondary
| Measure | Time frame |
|---|---|
| Safety, Tolerability, the Pharmacokinetics, a Recommended Dose (RD) for Phase II Clinical Study and the Anti-tumor Effect in Evaluable Subjects. | 3 weeks |
Countries
Japan
Participant flow
Recruitment details
This study was recruited at 1 center in Japan during the period of May 2006 to Jan 2008
Participants by arm
| Arm | Count |
|---|---|
| E7389 E7389 will be administered intravenously on Days 1 and 8 of a 21-day cycle. Initial dose level will be 0.7 mg/m\^2, with planned dose levels of 1.0, 1.4, & 2.0 mg/m\^2. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive Disease | 1 |
Baseline characteristics
| Characteristic | E7389 |
|---|---|
| Age Continuous | 58.1 years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 15 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 5 / 15 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD was the lowest dose at which a dose limiting toxicity occurred.
Time frame: 3 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7389 | Maximum Tolerated Dose (MTD) | 2.0 mg/m^2 |
Primary
Number of Subjects Who Experienced Dose Limiting Toxicity (DLT)
DLT is an adverse drug reaction defined as 1)Grade 4 neutropenia for 5 days, 2)\>/=Grade 3 febrile neutropenia, 3)\>/=Grade 3 neutropenia requiring iv antibiotics, 4)Grade 4 thrombocytopenia, 5)\>/=Grade 3 nonhematologic toxicity, 6)Omission of study drug on Day 8 due to \>/=Grade 3 neutropenia or thrombocytopenia or investigator decision.
Time frame: 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7389 | Number of Subjects Who Experienced Dose Limiting Toxicity (DLT) | 5 participants |
Secondary
Safety, Tolerability, the Pharmacokinetics, a Recommended Dose (RD) for Phase II Clinical Study and the Anti-tumor Effect in Evaluable Subjects.
Time frame: 3 weeks