An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01773421
First received: January 17, 2013
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

This study consists of two Parts. Part A (Food Effect Study) and Part B (Determination of MTD for BID Dosing).Part A will be initiated first, and Part B will be initiated after the PK results of Part A have been evaluated.


Condition Intervention Phase
Advanced Solid Tumors
Drug: E7820
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820, to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • The effect of a high fat meal on oral bioavailability of 50 mgE7820 in comparison with fasting conditions [ Time Frame: 28-day cycles ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part B MTD Twice Daily (BID) Dosing Schedule:The maximum tolerated dose (MTD) of E7820 administered orally, twice daily (BID). [ Time Frame: 28-day cycles ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: July 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A Drug: E7820

FOOD EFFECT STUDY:

Each subject (a minimum of 12 subjects) will be assigned according to a randomization code to receive a single 50 mg dose of E7820 on Day 1, either after fasting for 10 hours, or immediately after consuming a high fat breakfast. Following a 7-day washout period, the subjects will crossover and a second 50 mg dose of E7820 will be administered on Day 8.

Experimental: Part B Drug: E7820

MTD DETERMINATION FOR BID DOSING SCHEDULE

The initial dose of E7820 will be 50 mg BID. If allowed by the rules for dose escalation,the dose escalations will be to 60 mg BID, 80 mg BID, and 100 mg BID.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 less than or equal to 2
  4. Subjects with known brain metastases will be eligible under the following conditions A. Have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of brain disease recurrence or B. Have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of brain disease progression and C. Are asymptomatic and D. Discontinued corticosteroid treatment at least 30 days prior to Cycle 1, Day 1
  5. Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN) In case alkaline phosphatase is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
  6. Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (177 micro-mol/L) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula
  7. Provide written informed consent.
  8. Are willing and able to comply with all aspects of the protocol.
  9. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than or equal to 9 g/dL (5.5 mmol/L) and platelet count greater than or equal to 100 x 109/L.
  10. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [beta-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  11. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
  12. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females 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.
  13. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.

Exclusion Criteria:

  1. Leptomeningeal metastases or brain metastases (except as for inclusion criteria #4).
  2. Active hemoptysis (at least 2.5 mL [0.5 teaspoon] bright red blood) within 3 weeks prior to the first dose of study drug.
  3. Hypersensitivity to sulfonamide derivatives.
  4. Subjects who have had radiation to greater than or equal to 30% of their bone marrow.
  5. Subjects who require therapeutic anti-coagulant therapy with warfarin or related vitamin K 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 less than 50% on echocardiography or MUGA scanning.
  7. Anticancer therapies that have not been completed at least 28 days (42 days in the case of mitomycin C or nitrosoureas) prior to treatment with E7820 (other than surgery or treatment with a protein kinase inhibitor which must have been completed no less than one week prior to treatment with E7820).
  8. Incomplete recovery from previous radiotherapy, chemotherapy, or surgery other than residual cutaneous effects or stable less than Grade 2 gastrointestinal toxicity.
  9. History of an ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months before study entry.
  10. A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolongation of QTc interval greater than 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 (Appendix 6).
  15. Subjects who have a positive test result for human immunodeficiency virus (HIV), hepatitis A, hepatitis B or hepatitis C.
  16. Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior 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. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
  20. Use of illegal recreational drugs.
  21. Any medical or other condition that, in the opinion of the investigator, would preclude the subject's participation in a study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01773421

Locations
Netherlands
Netherlands Cancer Institute
Amsterdam, Netherlands
University Medical Centre Utrecht
Utrecht, Netherlands
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
University College London Hospital
London, United Kingdom
The Christie Hospital
Manchester, United Kingdom
Sir Bobby Robson Cancer Trials Research Centre
Newcastle, United Kingdom
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Larisa Reyderman Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01773421     History of Changes
Other Study ID Numbers: E7820-E044-110
Study First Received: January 17, 2013
Last Updated: April 21, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014