Advanced Solid Tumors
Conditions
Keywords
Metastatic Tumors, Advanced Solid Tumors, Stage IV Tumors, Solid Tumors, Recurrent Solid Tumors
Brief summary
To determine the maximum tolerated dose of E7389 in patients with advanced solid tumors that have progressed following standard therapy or for which no standard therapy exists.
Interventions
DRUGE7389
E7389 Dose-escalation starting at 0.25 mg/m\^2 intravenous on Days 1, 8, and 15 of a 28 day cycle.
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 * 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 \<1.5mg/dL or creatinine clearance \>= 45mL/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 \< 1.5mg/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 times ULN * 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 active anti-coagulant therapy * 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 uncontrolled cardiovascular illness defined as unstable angina, myocardial infarction within 6 months prior to study entry, symptomatic congestive heart failure (CHF) (NYHA II or higher) clinical evidence of CHF, or clinical evidence of serious cardiac arrhythmia * 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 |
|---|---|
| Determination of the Maximum Tolerated Dose | 28 Days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E7389 E7389 Dose-escalation starting at 0.25 mg/m\^2 intravenous on Days 1, 8, and 15 of a 28 day cycle. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Discon Therapy | 3 |
| Overall Study | Progressive Disease | 23 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | E7389 |
|---|---|
| Age Continuous | 57.4 years STANDARD_DEVIATION 11.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 12 / 32 |
Outcome results
Primary
Determination of the Maximum Tolerated Dose
Time frame: 28 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7389 | Determination of the Maximum Tolerated Dose | 1.0 mg/m^2 |