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A Phase 1, Two-Arm, Open-Label Study of E7974 Administered on Days 1, 8, and 15 of a 28-Day Cycle and Days 1 and 8 of a 21-Day Cycle in Patients With Solid Malignancies

Phase 1
18 Years
Not Enrolling
Solid Tumor Malignancies, Cancer

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Trial Information

A Phase 1, Two-Arm, Open-Label Study of E7974 Administered on Days 1, 8, and 15 of a 28-Day Cycle and Days 1 and 8 of a 21-Day Cycle in Patients With Solid Malignancies

This is a two-arm, open-label, non-randomized, dose-escalation study to determine the MTD of
E7974 administered as an intravenous bolus dose on Days 1, 8, and 15 of a 28-day cycle (Arm
A) or on Days 1 and 8 of a 21-day cycle (Arm B) to patients with solid tumors that have
progressed following effective therapy or for which no effective therapy exists. Response
and progression will be evaluated in this study using Response Evaluation Criteria In Solid
Tumors (RECIST) criteria.

Inclusion Criteria:

Patients who meet all of the inclusion criteria and none of the exclusion criteria will be
eligible for entry into the study:

1. Patients must have a pathologically diagnosed, histologically or cytologically
confirmed solid tumor that has progressed following effective therapy or for which no
effective therapy exists (including surgery or radiation therapy).

2. Patients must be >= 18 years of age.

3. Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.

4. Patients must have a life expectancy of >= 3 months.

5. Patients must have adequate renal function as evidenced by serum creatinine <= 1.5
mg/dL or creatinine clearance >= 40 mL/minute (min).

6. Patients must have adequate bone marrow function as evidenced by absolute neutrophil
count >= 1,500/µL, hemoglobin of >= 9 g/dL (may be transfused), and platelet count
(not transfused) >= 100,000/µL.

7. 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.

8. 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.

9. Patients must be willing and able to undergo blood draw and urine sampling for PK in
Cycle 1.

10. Patients may have either measurable or non-measurable disease.

Exclusion Criteria:

The presence of one or more of the following criteria will disqualify a patient from
enrollment in the study:

1. Patients who have received chemotherapy within three weeks of E7974 treatment start
(6 weeks for a nitrosourea).

2. Patients who have not recovered from any chemotherapy-related or other
therapy-related toxicity to <= Grade 1 at study entry (excluding Grade 2 alopecia).

3. 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).

4. Patients who have had major surgery without full recovery or major surgery within
three weeks of E7974 treatment start.

5. Patients with primary brain tumors or metastasis at study entry must have controlled
them for >= 1 month by previous treatment, including radiation therapy and

6. Women who are pregnant or breastfeeding.

7. Women of childbearing potential with either a positive pregnancy test at screening or
no pregnancy test.

8. Women of childbearing potential unless (1) surgically sterile, (2) physiologically
postmenopausal for > 12 months, or (3) using adequate measures (including barrier
methods) of contraception.

9. Fertile men or their partners who are not willing to use contraception.

10. Patients who have a positive history for Human Immunodeficiency Virus (HIV) and/or
have active hepatitis B or active hepatitis C at study entry.

11. Patients with severe, uncontrolled intercurrent illness or infection.

12. 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.

13. Patients who have received organ allografts requiring immunosuppressive therapy.

14. 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.

15. Patients with a current history of peripheral neuropathy > CTC Grade 2 (e.g.,
diabetic or chemotherapy-induced neuropathy).

16. Patients with a history of uncontrolled seizures.

17. Patients with marked baseline prolongation of QT/QTc interval (QTc interval >470)
using the Fridericia method as the main method of QTc analysis.

18. Patients with other significant diseases or disorders that, in the Investigator's
opinion, would exclude them from the study.

19. Patients with allergy or hypersensitivity to hemiasterlin based product or analogue.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the maximum tolerated dose of E7974 in patients with solid malignancies.

Outcome Time Frame:

Duration of each cycle will be 28 or 21 days; patients will attend a follow-up visit 30 days after last study treatment. Follow-up for safety and efficacy will occur 6 months after the last patient is accrued to the study.

Safety Issue:


Principal Investigator

Jenny Zhang, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Eisai Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

July 2005

Completion Date:

October 2009

Related Keywords:

  • Solid Tumor Malignancies, Cancer
  • Neoplasms



Indiana University Indianapolis, Indiana  46202
CTRC San Antonio, Texas  78229