A Dose-Finding Study of E7050 Administered Orally to Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00869895
First received: March 25, 2009
Last updated: November 5, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD) of E7050 given orally in patients with advanced solid tumors.


Condition Intervention Phase
Cancer
Drug: E7050
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose-Finding Study of E7050 Administered Orally to Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose: the highest dose at which no more than 1 out of 6 patients experiences Dose Limiting Toxicity (DLT) during Cycle 1. [ Time Frame: Weekly assessments during the first 4 weeks of treatment. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • DLTs and adverse events. [ Time Frame: Weekly assessments during the first 4 weeks of treatment for DLTs and throughout the study for AEs. ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (blood and urine). [ Time Frame: Weekly assessments of blood during Cycle 1 and every 2 weeks for subsequent cycles and of urine on Day 1 of Cycles 1 and 2. ] [ Designated as safety issue: No ]
  • Pharmacodynamics (blood). [ Time Frame: Weekly assessments during Cycle 1, every 2 weeks on Cycle 2, and on Day 1 of subsequent cycles. ] [ Designated as safety issue: No ]
  • Best overall tumor response, duration of response and duration of stable disease assessed according to modified RECIST (Response Evaluation Criteria in Solid Tumors). [ Time Frame: At Screening, between Days 21 and 28 of every even cycle, and at the Final Visit. ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: March 2009
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: E7050
Oral dosing starting at 100 mg once daily. After the MTD of once daily dosing has been determined, subsequent cohorts will be treated with a divided dosing schedule either twice or three times daily. The starting dose for this schedule will be an appropriate level below the MTD for once daily dosing.

  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.
  2. Histologically and/or cytologically confirmed metastatic solid tumors, that have progressed after treatment with approved therapies, or for which there are no standard effective therapies available.
  3. Adequate bone marrow function.
  4. Adequate renal function.
  5. Adequate liver function.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  7. Life expectancy > 3 months.
  8. Be willing and able to comply with the study protocol, and can give written informed consent.

    Additional inclusion criterion for the additional 15 patients recruited to the expanded MTD cohort only:

  9. At least one tumor lesion with diameter >= 2 cm measurable according to Modified RECIST.

Exclusion Criteria:

  1. Any condition that may preclude oral intake or oral absorption, history of gastrointestinal malabsorption, or surgery involving gastro- and/or intestinal- anastomosis within 4 weeks prior to starting study drug.
  2. Untreated or unstable known primary or metastatic central nervous system (CNS) tumors (stability shown by contrast-enhanced computed tomography or magnetic resonance imaging scans at least 8 weeks apart, with the most recent scan obtained within 28 days prior to starting study treatment).
  3. Known human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infection or intercurrent illness (unrelated to tumor).
  4. Prior surgery, radiotherapy, chemotherapy, biologic therapy or investigational drugs within 4 weeks prior to starting study drug. Prior immunotherapy, hormonal, or molecular targeted therapy within 2 weeks prior to starting study treatment (except gonadorelin analogue therapy for prostate cancer is allowed). (All acute toxicities related to prior treatments should have resolved).
  5. Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within 6 months prior to starting study drug.
  6. Requiring therapeutic anti-coagulant therapy (prophylactic dose of heparin or low molecular weight heparin is allowed).
  7. Poorly controlled hypertension (defined as a change in hypertensive therapy within 3 months of starting study drug) or hypertension diagnosed at screening (defined as a repeat blood pressure measurement of 160/90 mmHg or higher).
  8. Pregnancy or lactation. Female patients of childbearing potential must have a negative pregnancy test before inclusion into the study, and must agree to use medically acceptable methods of contraception (e.g. abstinence, or a double-barrier method [e.g. condom + spermicide, condom + diaphragm with spermicide], or IUD, or have a vasectomised partner) starting at Screening and throughout the entire study period and for 2 months after the last dose of study drug. Those female patients using hormonal contraceptives must also be using an additional approved method of contraception (as described previously) starting at Cycle 1 Day 1, and continuing throughout the entire study period and for 2 months after the last dose of study drug.

    Perimenopausal women must have been amenorrheic for at least 12 months; otherwise a pregnancy test is required.

    Male patients must agree to use contraceptive methods (e.g., abstinence, or a double-barrier method [e.g., condom + spermicide, condom + partner diaphragm with spermicide]).

    Additional exclusion criterion for the additional 15 patients recruited to the expanded MTD cohort only:

  9. History of any malignancy other than the present malignancy (except treated non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 5 years.
  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: NCT00869895

Locations
United Kingdom
Christie Hospital
Manchester, United Kingdom, M20 4BX
Royal Marsden Hospital
Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Wouter Hanekom Eisai Limited
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00869895     History of Changes
Other Study ID Numbers: E7050-E044-101
Study First Received: March 25, 2009
Last Updated: November 5, 2012
Health Authority: European Union: European Medicines Agency

Keywords provided by Eisai Inc.:
Advanced solid tumors

ClinicalTrials.gov processed this record on July 29, 2014