Status:

COMPLETED

A Phase 1 Open-Label Study of E7974 Administered on Days 1 and 15 of a 28-Day Cycle in Patients With Solid Malignancies

Lead Sponsor:

Eisai Inc.

Conditions:

Cancer, Malignant Tumors

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) of E7974 administered on Days 1 and 15 of a 28-day cycle in subjects with solid malignancies that have progressed following e...

Eligibility Criteria

Inclusion

  • Patients who meet all of the inclusion criteria and none of the exclusion criteria will be eligible for entry into the study:
  • Patients must have a pathologically diagnosed, histologically or cytologically confirmed solid malignancy that has progressed following effective therapy or for which no effective therapy exists (including surgery or radiation therapy).
  • Patients must be \>= 18 years of age.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0, 1 or 2.
  • Patients must have a life expectancy of \>= 3 months.
  • Patients must have adequate renal function as evidenced by serum creatinine \<= 1.5 mg/dL or creatinine clearance \>= 40 mL/minute (min)
  • Patients must have adequate bone marrow function as evidenced by absolute neutrophil count \>= 1,200/µL, hemoglobin of \>= 9 g/dL (may be transfused), and platelet count (not transfused) \>= 100,000/µL.
  • Patients must have adequate liver function as evidenced by bilirubin \<= 1.5 mg/dL and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 3 times the upper limits of normal (ULN), unless related to liver involvement by tumor, in which case \<= 5.0 times ULN.
  • Patients must be willing and able to sign written informed consent and be able to comply with the study protocol for the duration of the study.
  • Patients must be willing and able to undergo blood draw and urine sampling for PK in Cycle 1.
  • Patients may have either measurable or non-measurable disease.
  • For Prostate Cancer patients only being enrolled at the MTD expansion phase:
  • Males with histologically proven adenocarcinoma of the prostate that has progressed (i.e. a minimum of three successive baseline values to document two consecutive rises in Prostate Specific Antigen (PSA) (with the last value 5 ng/mL) taken at least one week apart prior to study entry) despite castration or maintenance of castrate-level testosterone (defined as serum testosterone 50 ng/dL or 1.7 nmol/L), during non-hormonal chemotherapy.
  • Patients must have failed at least one previous chemotherapeutic regimen with tubulin binding agents such as docetaxel.

Exclusion

  • The presence of one or more of the following criteria will disqualify a patient from enrollment in the study:
  • Patients who have received chemotherapy within three weeks of E7974 treatment start (6 weeks for a nitrosourea).
  • Patients who have not recovered from any chemotherapy-related or other therapy-related toxicity to \<= Grade 1 at study entry (excluding Grade 2 alopecia).
  • Patients who have received radiotherapy \<= 3 weeks prior to study enrollment, whose marrow exposure has exceeded 25% and who have not recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
  • Patients who have had major surgery without full recovery or major surgery within three weeks of E7974 treatment start.
  • Patients with primary brain tumors or metastasis at study entry must have controlled them for \>= 1 month by previous treatment, including radiation therapy and corticosteroids.
  • Women who are pregnant or breastfeeding.
  • Women of childbearing potential with either a positive serum pregnancy test at screening or no pregnancy test.
  • Women of childbearing potential unless (1) surgically sterile, (2) physiologically postmenopausal for \>= 12 months, or (3) using adequate measures (including barrier methods) of contraception.
  • Fertile men or their partners who are not willing to use contraception.
  • Patients who have a history of positive testing for Human Immunodeficiency Virus (HIV) and/or have active hepatitis B or active hepatitis C at study entry.
  • Patients with severe, uncontrolled intercurrent illness or infection.
  • Patients with medically uncontrolled cardiovascular illness defined as unstable angina, \>= symptomatic Grade II New York Heart Association (NYHA) Classification congestive heart failure (CHF), or myocardial infarction within six months prior to study entry.
  • Patients who have received organ allografts requiring immunosuppressive therapy.
  • Patients who have received investigational drugs including immunotherapy, gene therapy, hormone therapy, biologic therapy, or chemotherapy within the three-week period prior to E7974 treatment start; patients must have recovered from any previous major therapy-related toxicities (Grade 3 or 4) to \<= Grade 1 at study entry (excluding Grade 2 alopecia).
  • Patients with a current history of peripheral neuropathy \> CTC Grade 1 (e.g., diabetic or chemotherapy-induced neuropathy).
  • Patients with a history of uncontrolled seizures.
  • Patients with marked baseline prolongation of QT/QTc interval (QTc interval \>470) using the Fridericia method as the main method of QTc analysis.
  • Patients with other significant diseases or disorders that, in the Investigator's opinion, would exclude them from the study.
  • Patients with allergy or hypersensitivity to hemiasterlin based product or analogue.

Key Trial Info

Start Date :

January 1 2006

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

August 1 2009

Estimated Enrollment :

30 Patients enrolled

Trial Details

Trial ID

NCT00130169

Start Date

January 1 2006

End Date

August 1 2009

Last Update

July 1 2015

Active Locations (2)

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Page 1 of 1 (2 locations)

1

Nevada Cancer Institute

Las Vegas, Nevada, United States, 89135

2

University Hospital Medical Center - SUNY at Stony Brook

Stony Brook, New York, United States, 11794