Cancer
Conditions
Keywords
Cancer, tumors
Brief summary
The malignancies (advanced solid tumors) that have been chosen for evaluation of E7389 are those where E7389 has demonstrated significant pre-clinical anti-tumor activity, both in vitro and in vivo. The ultimate goal is to demonstrate the clinical activity of E7389 in the treatment of these, and potentially other, tumor types.
Interventions
DRUGE7389
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a histologically or cytologically confirmed and measurable advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy) * Patients may have received prior chemotherapy (limit of two prior chemotherapy regimens) * Patients must be aged \>= 18 years * Patients must have a Karnofsky Performance Status of \> 70% -- 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 \> 60 mL/minute * Patients must have adequate bone marrow function as evidenced by absolute neutrophil count \> 1,500/µL and platelets \> 100,000/µL * Patients must 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 * Patients must be willing and able to comply with the study protocol for the duration of the study * Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
Exclusion criteria
* Patients who have received chemotherapy within three weeks (six weeks if nitrosoureas were received) of E7389 treatment start * Patients who have not recovered from any chemotherapy related or other therapy related toxicity at study entry * Patients who require therapeutic doses of anti-coagulant therapy (eg, Coumadin, heparin, low molecular weight heparin). Low doses of anticoagulants used for patency (e.g., lines, catheters, ports) are permitted. * Women who are pregnant or breastfeeding. * Women 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) using adequate measures of contraception in the opinion of the Investigator (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) * Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception * Patients who have not successfully completed local therapy for previously treated central nervous system (CNS) metastases and who have not been discontinued from corticosteroids for at least four weeks before starting treatment with E7389. Patients with asymptomatic brain metastases who have no evidence of midline shift on CT scan or MRI may be enrolled without initiation of local therapy for the CNS metastases. In this case, a repeat scan must be performed within four weeks of the original scan to ensure that disease progression is not occurring. * Patients who have tested positive for HIV * Patients with severe uncontrolled intercurrent illness/infection (excluding malignancies) * Patients with cardiovascular impairment * Patients with organ allografts * Patients who have received investigational drugs, including immunotherapy, gene therapy, hormone therapy, or other biologic therapy; anti-neoplastic therapy; or radiation therapy (other than required for palliation) within three weeks of E7389 treatment start * Patients who have had major surgery within four weeks of E7389 treatment start without a full recovery * Patients with a hypersensitivity to Halichondrin B and/or Halichondrin B-like compounds Patients with other significant disease that, in the Investigator's opinion, would exclude the patient from the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used. | 12 Weeks |
Countries
United States
Participant flow
Recruitment details
This study was recruited at 2 centers in U.S.during the period of Aug 2003 to Apr 2005.
Participants by arm
| Arm | Count |
|---|---|
| E7389 Dose-Escalating E7389 dose-escalation starting at 0.25 mg/m\^2 intravenous on Day 1 of a 21 day cycle. Dose escalations scheme used a two part design and proceeded based on dose-limiting toxicity and maximum tolerated dose. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive Disease | 15 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | E7389 Dose-Escalating |
|---|---|
| Age, Customized Mean (+/- Standard Deviation) | 59.0 participants STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 3 participants |
| Race/Ethnicity, Customized More than one race | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 participants |
| Race/Ethnicity, Customized White | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 21 |
| serious Total, serious adverse events | 10 / 21 |
Outcome results
Primary
Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used.
Time frame: 12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| E7389 Dose-Escalating | Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used. | partial response | 1 participants |
| E7389 Dose-Escalating | Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used. | stable disease | 12 participants |
| E7389 Dose-Escalating | Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used. | progressive Disease | 7 participants |