Solid Tumors
Conditions
Interventions
This study consists of three Parts. Part A (Food Effect Study), Part B
(Determination of MTD for QD Dosing), and Part C (Determination of MTD
for BID Dosing).
Part A will be initiated first. Parts B
Sponsors
Eisai
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older. 2. Histological or cytological evidence of an unresectable or refractory solid tumor. 3. Eastern Cooperative Oncology Group (ECOG) performance status 3 x ULN (in absence of liver metastases) or >5 x ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific alkaline phosphatise must be separated from the total and used to assess the liver function instead of the total alkaline phosphatise. 5. Adequate renal function as evidenced by serum creatinine =40 mL/min per the Cockcroft and Gault formula. 6. Provide written informed consent. 7. Are willing and able to comply with all aspects of the protocol. 8. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >=1.5 x 109/L, hemoglobin >=9 g/dL (5.5 mmol/L) and platelet count >=100 x 109/L. 9. All females must have a negative serum ß-hCG test result or a negative urine pregnancy test results at Screening and Baseline. Females of child-bearing potential must agree to use a medically acceptable method of contraception (e.g., abstinence, an intrauterine device [IUD], a highly effective method of contraception such as condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, an oral contraceptive or have a vasectomised partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal women (defined as greater than age 50 and at least 12 months of amenorrhea) or subjects who have been sterilized surgically (i.e., as a result of tubal ligation, hysterectomy or bilateral oophorectomy) or who are otherwise proven sterile. All women who are of reproductive potential and who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. 10. Male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, an IUD) beginning at least 1 menstrual cycle prior to starting study drug(s), throughout the entire study period, and for 30 days after the last dose of study drug, unless they are sexually abstinent or have undergone a successful vasectomy. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). Additional Inclusion Criterion Specific for Part B and C Expansion Cohorts Only 11. Subjects must have at least one metastatic lesion, EITHER >= 3 cm in the lung or liver OR a lesion >=2 cm in other parts of the body that are less subject to motion with breathing. The existence of an appropriately sized lesion should be determined on the basis of the pretreatment CT scan.
Exclusion criteria
Exclusion criteria: 1. Central nervous system metastases. 2. Hemoptysis. 3. Hypersensitivity to sulfonamide derivatives. 4. Subjects who have had radiation to >=30% of their bone marrow . 5. Subjects who require therapeutic anti-coagulant therapy with warfarin or related vitamin antagonists. Prophylactic doses of heparin or low molecular weight heparin or thrombin inhibitors may be used in place of warfarin. 6. Left ventricular ejection fraction 480 msec. 11. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject*s safety or study conduct. 12. Concurrent treatment with CYP3A4 inhibitors such as verapamil, cyclosporin, quinidine, erythromycin, mibefradil, clarithramycin and azoles . 13. Concurrent treatment with drugs known to be extensively metabolized by CYP2C9 and/or CYP2C19 14. Chronic treatment with known inducers of CYP3A4 within four weeks of receiving treatment with E7820 other than corticosteroids. 15. Subjects who have a positive test result for human immunodeficiency virus (HIV), hepatitis A, hepatitis B or hepatitis C. 16. Suffering from psychotic disorder(s) and/or unstable recurrent affective disorder(s) evident by use of antipsychotics or have had a suicide attempt(s) within approximately the last 2 years. 17. History of drug or alcohol dependency or abuse within approximately the last 2 years. 18. Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors. 19. Subjects with meningeal carcinomatosis. 20. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen. 21. Use of recreational drugs. 22. Any history of or concomitant medical condition that, in the opinion of the Investigator, would compromise the subject*s ability to safely complete the study Additional Exclusion Criteria Specific for Parts B and C Expansion Cohorts Subjects enrolled in the Expansion Cohort of Parts B and C of the study are excluded from DCE-MRI/DWI-MRI procedures for the following reasons: 1. Cardiac pacemaker 2. Ferromagnetic metal implants other than those approved as safe for use in MRI scanners (e.g., aneurysm clips, shrapnel) 3. Obesity exceeding equipment limits 4. Inability to tolerate DCE-MRI/DWI-MRI scanning procedure 5. History of severe allergic reaction to MR contrast agent
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Determination of the safety and tolerability of E7820 administered QD. Determination of the pharmacokinetics of E7820 administered Assessment of evidence of efficacy by RECIST 1.1 | — |
Primary
| Measure | Time frame |
|---|---|
| Part A: Determination of effect of food on disposition of E7820 Part B: Determination of MTD for once-daily dosing Part C: Determination of MTD for twice-daily dosing | — |
Countries
Netherlands
Outcome results
None listed