Non-Small-Cell Lung Carcinoma
Conditions
Brief summary
This is a study of E7389 in patients with recurrent and/or metastatic Non-Small-Cell Lung Cancer (NSCLC) who progressed during or after treatment with a platinum agent and another chemotherapy.
Interventions
DRUGE7389 28 Day Cycle
E7389 1.4 mg/m\^2 IV bolus on Days 1, 8, and 15 of a 28 day cycle.
DRUGE7389 21 Day Cycle
E7389 1.4 mg/m\^2 IV bolus on Days 1 and 8 of a 21 day cycle.
Sponsors
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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 diagnosis of non-small cell lung cancer with at least one site of measurable disease by the RECIST criteria. * Patients must have failed prior platinum-containing doublet chemotherapy. Patients who have received single agent chemotherapy with or without a subsequent taxane containing regimen may be enrolled after discussion with Sponsor. * Patients must be ≥ 18 years of age. * Patients must have a performance score of 0 or 1 using the ECOG performance scale. * Patients must have a life expectancy of ≥ 3 months. * Patients must have adequate renal function as evidenced by a serum creatinine ≤ 2.0 mg/dL or a calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula. * Patients must have adequate hepatic function as evidenced by bilirubin ≤1.5 mg/dL and alkaline phosphatase, AST and ALT ≤ 3 times upper limit of normal, unless there is evidence of liver metastases, in which case the alkaline phosphatase, AST and ALT must be ≤ 5 times upper limit of normal. * Patients must have adequate bone marrow function as evidenced by absolute neutrophil counts (ANC) ≥ 1.5 X 10\^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin \< 10.0 g/dL would be acceptable if it can be corrected by growth factor or transfusion), and platelet count ≥ 100 X 10\^9/L. * Patients must be willing and able to comply with the protocol guidelines for the duration of the study. * Patients must be willing and able to complete the Lung Cancer Symptom Scale (LCSS) instrument. * The biopsy specimen (paraffin block or at least 10 unstained slides) must be available from either the initial diagnosis or any subsequent diagnostic or surgical procedure of patients participating in the pharmacogenomics sub-study only. However, no additional biopsies are obligatory for participation in this study except those required for confirmation of the diagnosis. * 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 with pre-existing peripheral neuropathy \> Grade 2 * Patients who require therapeutic doses of warfarin * Patients who have not recovered from any chemotherapy, radiation or other therapy related toxicity deemed to be clinically significant at study entry * Patients with active symptomatic brain metastases. Patients with central nervous system (CNS) metastases are considered eligible if they have had adequately treated brain metastases, i.e. have completed treatment (tapered off steroids) at least four weeks before starting treatment with E7389. Patients who have no evidence that the metastases are symptomatic or actively growing (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. It is not the intention of this study to treat patients with active brain metastases. * Patients who have a positive history for HIV, active hepatitis B or active hepatitis C. * Patients with other significant medical, or psychiatric disorders that, in the opinion of the investigator, will exclude the patient from the study for compliance or safety reasons * Patients who have received investigational drugs, including immunotherapy, gene therapy, hormone therapy (except megestrol acetate for appetite stimulation), or other biological therapy; conventional chemotherapy or radiation therapy (except for palliation, defined as less than 10% of the bone marrow reserve and less than 20 Gy), within three weeks of E7839 enrollment * Patients who have received non-cytotoxics (eg, gefitinib, erlotinib) within one week of E7389 enrollment * Patients who have not recovered from major surgery within three weeks of E7389 enrollment * Patients with severe/uncontrolled intercurrent illness/infection * Patients with significant cardiovascular impairment (history of congestive heart failure\>NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia) * Patients with organ allografts * Patients with hypersensitivity to halichondrin B and/or halichondrin B-related compounds * Patients who participated in a prior E7389 clinical trial * Patients with second malignancy within the past 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma of the skin * Women who are pregnant or breast-feeding; woman of childbearing potential with 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. Perimenopausal women must be amenorrheic for at least 12 months or using adequate contraception 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response Rate (ORR) | From start of treatment until disease progression or recurrence | Based on Response Evaluation Criteria in Solid Tumors (RECIST), consisting of complete response (CR) plus partial response (PR). Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From time of CR or PR until recurrence or progressive disease | Measured from the time that measurement criteria were met for complete response (CR) and partial response (PR) until the first date that recurrence or progressive disease was objectively documented. |
| Progression Free Survival | From start of study medication until progressive disease or death | Defined as the time from the start of study medication until progressive disease or death from any cause during the study period. |
| Overall Survival | From time of start of study medication until death | Defined as the time from the start of study medication until death from any cause. |
Countries
United States
Participant flow
Recruitment details
This study was recruited at 29 centers in the US during the period of Dec 2004 to Apr 2006.
Participants by arm
| Arm | Count |
|---|---|
| E7389 28 Day Cycle E7389 1.4 mg/m\^2 intravenous bolus on Days 1, 8 and 15 of a 28 day cycle. | 77 |
| E7389 21 Day Cycle E7389 1.4 mg/m\^2 intravenous bolus on Days 1 and 8 of a 21 day cycle. | 26 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 2 |
| Overall Study | Other | 5 | 2 |
| Overall Study | Physician Decision | 7 | 5 |
| Overall Study | Progressive Disease | 44 | 18 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | E7389 28 Day Cycle | Total | E7389 21 Day Cycle |
|---|---|---|---|
| Age Continuous | 62.0 years STANDARD_DEVIATION 10.59 | 62.9 years STANDARD_DEVIATION 10.28 | 65.5 years STANDARD_DEVIATION 8.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 101 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 65 Participants | 89 Participants | 24 Participants |
| Region of Enrollment United States | 77 participants | 103 participants | 26 participants |
| Sex: Female, Male Female | 38 Participants | 52 Participants | 14 Participants |
| Sex: Female, Male Male | 39 Participants | 51 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 77 | 26 / 26 |
| serious Total, serious adverse events | 33 / 77 | 11 / 26 |
Outcome results
Primary
Overall Objective Response Rate (ORR)
Based on Response Evaluation Criteria in Solid Tumors (RECIST), consisting of complete response (CR) plus partial response (PR). Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
Time frame: From start of treatment until disease progression or recurrence
Population: Intent to Treat/Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7389 28 Day Cycle | Overall Objective Response Rate (ORR) | 11.7 percentage of participants |
| E7389 21 Day Cycle | Overall Objective Response Rate (ORR) | 3.8 percentage of participants |
Secondary
Duration of Response
Measured from the time that measurement criteria were met for complete response (CR) and partial response (PR) until the first date that recurrence or progressive disease was objectively documented.
Time frame: From time of CR or PR until recurrence or progressive disease
Population: Intent to Treat/Safety Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E7389 28 Day Cycle | Duration of Response | 171 Days |
| E7389 21 Day Cycle | Duration of Response | 176 Days |
Secondary
Overall Survival
Defined as the time from the start of study medication until death from any cause.
Time frame: From time of start of study medication until death
Secondary
Progression Free Survival
Defined as the time from the start of study medication until progressive disease or death from any cause during the study period.
Time frame: From start of study medication until progressive disease or death
Population: Intent to Treat/Safety Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E7389 28 Day Cycle | Progression Free Survival | 106 Days |
| E7389 21 Day Cycle | Progression Free Survival | 78 Days |