This is an open-label, non-randomized, dose-escalation study to determine the MTD of E7974 in a Day 1 of 21-day cycle in patients with advanced solid tumors that have progressed following effective therapy or for which no effective therapy exists. Toxicity parameters will be evaluated by the CTC 3.0 criteria. Response and progression will be evaluated in this study using RECIST criteria.

Condition	Intervention	Phase
Cancer, malignant tumors	Drug: HEAT	Phase III

Further Study Details: 

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• 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).
• Be >= 18 years of age.
• Have an ECOG status of 0, 1, or 2.
• Have a life expectancy of >= 3 months.
• Have adequate renal function as evidenced by serum creatinine <= 1.5 mg/dL or creatinine clearance >= 40 mL/minute.
• 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.
• Have adequate liver function as evidenced by bilirubin <= 1.5 mg/dL and alanine transaminase (ALAT) and aspartate transaminase (ASAT) <= 2 times the upper limits of normal (ULN), unless related to liver involvement by tumor, in which case <= 5.0 x ULN.
• Be willing and able to comply with the study protocol for the duration of the study, and give written informed consent.
• Be willing to undergo blood draw and urine sampling for PK in Cycle 1, and at any time in Cycle 2 when the dose of study drug may be lowered.
• Have not received more than four previous chemotherapy regimens in the advanced or metastatic setting. Prior adjuvant or hormonal/monoclonal antibody therapies are allowed and are not included when calculating the number or previous therapies.
• Can have either measurable or non-measurable disease.
• Women of child bearing potential must have negative pregnancy test.

Exclusion Criteria:

• Patients who have received chemotherapy within 3 weeks of E7974 treatment start; (six weeks for nitrosoureas).
• Patients who have not recovered from any chemotherapy-related or other therapy-related toxicity to <= Grade 1 at study entry; (Excluding alopecia grade 2).
• 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.
• 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 them controlled for >= one month by previous treatment, including radiation therapy and /or corticosteroids.
• Women who are pregnant or breastfeeding or of childbearing potential with either a positive pregnancy test at screening or no pregnancy test.
• 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.
• Fertile men or their partners who are not willing to use contraception.
• Patients who have a history of positive testing for HIV; active hepatitis B or active hepatitis C.
• Patients with severe uncontrolled intercurrent illness or infection.
• Patients with medically uncontrolled cardiovascular illness defined as unstable angina or congestive heart failure (CHF), with > symptomatic Grade II (NYHA Classification), or myocardial infarction within 6 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 therapyrelated toxicities at study entry.
• Patients with a current history of peripheral neuropathy > CTC Grade 1 (eg, diabetic or chemotherapy-induced neuropathy).
• Patients with a history of uncontrolled seizures.
• Patients with other significant diseases or disorders that, in the Investigator’s opinion, would exclude them from the study.
• Patients with marked screening or baseline prolongation QT/QTc interval (QTc interval > 470 mm) using the Frederica method as a main method of QTC analysis.

Please refer to this study by ClinicalTrials.gov identifier  NCT00165802

: Eisai Medical Services      1-888-422-4743; 1-888-274-2378 

Florida
      University of Miami and Sylvester Cancer Center, Miami,  Florida,  33136,  United States

Study chairs or principal investigators

Caio Lima,  Principal Investigator,  University of Miami and Sylvester Cancer Center   

Study ID Numbers:  E7974-A001-103
Last Updated:  September 13, 2005
Record first received:  September 12, 2005
ClinicalTrials.gov Identifier:  NCT00165802
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-20