A Phase I Open Label Study of E7974 Administered on Day 1 of a 21-Day Cycle In Patients With Advanced Solid Tumors
At this time, we are only enrolling patients for the MTD cohort that
meet all study entry criteria, plus the CRC criterion (Inclusion Criterion #12).Patients
who meet all of the inclusion criteria and none of the exclusion criteria will be eligible
for entry into the study. Patients must:
1. Have a histologically or cytologically confirmed advanced solid tumor that has
progressed following effective therapy or for which no effective therapy exists
(including surgery or radiation therapy).
2. Be >= 18 years of age.
3. Have an Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
4. Have a life expectancy of >= 3 months.
5. Have adequate renal function as evidenced by serum creatinine <= 1.5 mg/dL or
creatinine clearance >= 40 mL/minute.
6. 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. Have adequate liver function as evidenced by bilirubin <= 1.5 x ULN and alanine
transaminase (ALT) and aspartate transaminase (AST) <= 3 times the upper limits of
normal (ULN), unless related to liver involvement by tumor, in which case <= 5.0 x
8. Give written informed consent.
9. Be willing and able to comply with the study protocol for the duration of the study.
10. Be willing to undergo blood draw and urine sampling for PK in Cycle 1.
11. Can have either measurable or non-measurable disease.
12. If a CRC patient is being treated at the MTD, they must have <= 4 prior regimens in
the metastatic setting.
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 3 weeks of E7974 treatment start; (six
weeks for nitrosoureas).
2. Patients who have not recovered from any chemotherapy-related or other
therapy-related toxicity to < Grade 1 at study entry (excluding alopecia Grade 2).
3. Patients who have received radiotherapy <= 3 weeks prior to study enrollment, (prior
radiation therapy allowed to <25% of the bone marrow), and who have not recovered
from the toxic effects of the treatment prior to study enrollment (except for
alopecia). Lesions that have been radiated cannot be included as sites of measurable
disease unless clear tumor progression has been documented in these lesions since the
end of radiation therapy.
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 them
controlled for > one month by previous treatment, including radiation therapy and /or
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 or (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 history of positive testing 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 or congestive heart failure (CHF), with > symptomatic Grade II New York Heart
Association (NYHA) Classification, or myocardial infarction (MI) 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 toxicity (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 other significant diseases or disorders that, in the investigator's
opinion, would exclude them from the study.
18. Patients with marked screening or baseline prolongation QT/QTc interval (QTc interval
> 470 mm) using the Fridericia method as the main method of QTc analysis.
19. Patients with allergy or hypersensitivity to hemiasterlin based product or analogue.