A Phase 1 Open-Label Study of E7974 Administered on Days 1 and 15 of a 28-Day Cycle in Patients With Solid Malignancies
This study has been completed.
Information provided by:
First received: August 12, 2005
Last updated: November 10, 2009
Last verified: November 2009
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 effective therapy or for which no effective therapy exists.
Cancer, Malignant Tumors
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase 1 Open-Label Study of E7974 Administered on Days 1 and 15 of a 28-Day Cycle in Patients With Solid Malignancies
Primary Outcome Measures:
- Determine the maximum tolerated dose of E7974 in patients with solid malignancies. [ Time Frame: Duration of each cycle will be 28 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. ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Assess E7974 for safety, efficacy, pharmacokinetics and pharmacodynamics; evaluate the efficacy of E7974 in patients with metastatic, refractory prostate cancer. [ Time Frame: Duration of each cycle will be 28 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. ] [ Designated as safety issue: Yes ]
| Estimated Enrollment:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||August 2009 (Final data collection date for primary outcome measure)
Maximum Tolerated Dose defined as 0.35 mg/m^2 administered on Days 1 and 15 only of a 28-day cycle; the E7974 compound is administered as a bolus infusion; no placebo is given.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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 Criteria: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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00130169
|Nevada Cancer Institute
|Las Vegas, Nevada, United States, 89135 |
|University Hospital Medical Center - SUNY at Stony Brook
|Stony Brook, New York, United States, 11794 |
||Naseem Zojwalla, M.D.
No publications provided
||Peter Tarassoff, MD, Eisai Medical Research Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 12, 2005
||November 10, 2009
||United States: Food and Drug Administration
Keywords provided by Eisai Inc.:
ClinicalTrials.gov processed this record on March 25, 2015