Non-small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of chemotherapy followed sequentially by gefitinib versus chemotherapy alone in the first line treatment of non-small cell lung cancer (NSCLC). This study will be conducted in Asian patients who are classified as 'never smoker' since it is suggested that these patients are more likely to respond favorably to treatment with gefitinib.
Interventions
DRUGPemetrexed
500 milligrams per meter squared (mg/m2), administered by intravenous (IV) infusion every 21 days for 4 cycles (1-4) or 500 mg/m2, IV, every 21 days until disease progression or unacceptable toxicity.
DRUGCisplatin
75 mg/m2, IV, every 21 days for 4 cycles (1-4) or 75 mg/m2, IV, every 21 days for 4 cycles with optional continuation for 2 additional cycles until disease progression or unacceptable toxicity
DRUGGefitinib
250 mg, administered orally once daily beginning at Cycle 5 until disease progression or unacceptable toxicity
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic diagnosis non-small cell lung cancer (NSCLC) (Stage IIIB or IV) * Have not received any prior chemotherapy, molecular therapy, immunotherapy, biological therapy, or radiotherapy. Exception: palliative radiotherapy that is completed at least 4 weeks prior to study enrolment. * Have 'never smoked' (defined as having smoked \<100 cigarettes during his/her lifetime) * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Exclusion criteria
* Concurrent administration of any other tumor therapy * Other co-existing malignancies * Pregnancy or breast feeding * Serious concomitant disorders * Inability or unwillingness to take folic acid or vitamin B12 supplementation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline to first observation of disease progression or death, 12 weeks up to 31 months | Defined as the time from randomization to the first observation of disease progression, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tumor Response | Baseline to measured response or death, 12 weeks up to 31 months | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes not meeting above criteria. Responder is a participant exhibiting a best overall study response of CR or PR. |
| Duration of Response for Responders | Time of response to progressive disease or death, 12 weeks up to 31 months | The duration of a complete response (CR; the disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. A responder is a patient exhibiting a best overall study response of CR or PR. |
| Overall Survival | Baseline to date of death from any cause, 12 weeks up to 31 months | Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. Median overall survival could not be estimated as most participants were living at the end of the study. 25 participants from each treatment group were censored. In place of this outcome measure, the percentage of participants who died during the study are provided in the Post-Hoc Analysis Outcome Measure: Percentage of Participants Who Died During the Study. |
Countries
China, South Korea, Taiwan
Participant flow
Pre-assignment details
86 participants entered study. 13 participants were screen failures. 73 participants (40 pemetrexed/cisplatin/gefitinib and 33 pemetrexed/cisplatin) were assigned to treatment. 3 participants did not receive study drug. These 16 participants (13 screen failures and 3 that did not receive drug) were not included in the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed/Cisplatin/Gefitinib Pemetrexed 500 milligrams per meters squared (mg/m2) plus cisplatin 75 mg/m2 administered by intravenous (IV) infusion once every 3 weeks for 4 cycles without progression followed by gefitinib 250 mg administered orally, once daily, until disease progression or unacceptable toxicity. | 39 |
| Pemetrexed/Cisplatin Pemetrexed 500 milligrams per meters squared (mg/m2) plus cisplatin 75 mg/m2 administered by intravenous (IV) infusion once every 3 weeks for 4 cycles without progression followed by pemetrexed 500 mg/m2 administered by IV infusion (with optional cisplatin 75 mg/m2 for up to 2 additional cycles) until disease progression or unacceptable toxicity. | 31 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 15 | 6 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Pemetrexed/Cisplatin/Gefitinib | Pemetrexed/Cisplatin | Total |
|---|---|---|---|
| Age Continuous | 55.6 years STANDARD_DEVIATION 8.45 | 55.7 years STANDARD_DEVIATION 12.43 | 55.7 years STANDARD_DEVIATION 10.32 |
| Basis of Diagnosis Cytological | 9 Participants | 9 Participants | 18 Participants |
| Basis of Diagnosis Histopathological | 30 Participants | 22 Participants | 52 Participants |
| Disease Stage Stage IIIB | 6 Participants | 4 Participants | 10 Participants |
| Disease Stage Stage IV | 33 Participants | 27 Participants | 60 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 15 Units on a scale | 9 Units on a scale | 24 Units on a scale |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 24 Units on a scale | 22 Units on a scale | 46 Units on a scale |
| History of Smoking No | 39 Participants | 29 Participants | 68 Participants |
| History of Smoking Yes | 0 Participants | 2 Participants | 2 Participants |
| Pathological Diagnosis Adenocarcinoma | 30 Participants | 24 Participants | 54 Participants |
| Pathological Diagnosis Carcinoma, Squamous Cell | 7 Participants | 4 Participants | 11 Participants |
| Pathological Diagnosis Mixed Cell Carcinoma, Lung | 1 Participants | 1 Participants | 2 Participants |
| Pathological Diagnosis Non-Small Cell Lung Carcinoma | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized East Asian | 39 Participants | 31 Participants | 70 Participants |
| Region of Enrollment China | 16 participants | 14 participants | 30 participants |
| Region of Enrollment Korea, Republic of | 13 participants | 6 participants | 19 participants |
| Region of Enrollment Taiwan | 10 participants | 11 participants | 21 participants |
| Sex: Female, Male Female | 30 Participants | 25 Participants | 55 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 39 | 31 / 31 |
| serious Total, serious adverse events | 6 / 39 | 3 / 31 |
Outcome results
Primary
Progression-Free Survival (PFS)
Defined as the time from randomization to the first observation of disease progression, or death due to any cause.
Time frame: Baseline to first observation of disease progression or death, 12 weeks up to 31 months
Population: Randomized and treated (RT) population includes all randomized patients. Patients are analyzed according to the treatment they actually received (intent-to-treat \[ITT\] analysis). Patients were censored from this analysis (8 pemetrexed/cisplatin/gefitinib and 11 pemetrexed/cisplatin).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed/Cisplatin/Gefitinib | Progression-Free Survival (PFS) | 9.95 Months |
| Pemetrexed/Cisplatin | Progression-Free Survival (PFS) | 6.83 Months |
p-value: 0.0618Log Rank
Secondary
Duration of Response for Responders
The duration of a complete response (CR; the disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. A responder is a patient exhibiting a best overall study response of CR or PR.
Time frame: Time of response to progressive disease or death, 12 weeks up to 31 months
Population: Qualified for Response population includes all treated patients with measurable disease prior first dose of study therapy. Patients were censored for this analysis (2 pemetrexed/cisplatin/gefitinib and 2 pemetrexed/cisplatin).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed/Cisplatin/Gefitinib | Duration of Response for Responders | 12.29 Months |
| Pemetrexed/Cisplatin | Duration of Response for Responders | 4.14 Months |
Secondary
Number of Participants With Tumor Response
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes not meeting above criteria. Responder is a participant exhibiting a best overall study response of CR or PR.
Time frame: Baseline to measured response or death, 12 weeks up to 31 months
Population: Qualified for Response population includes all treated patients with measurable disease prior first dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed/Cisplatin/Gefitinib | Number of Participants With Tumor Response | 18 Participants |
| Pemetrexed/Cisplatin | Number of Participants With Tumor Response | 11 Participants |
p-value: 0.369Regression, Logistic
Secondary
Overall Survival
Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. Median overall survival could not be estimated as most participants were living at the end of the study. 25 participants from each treatment group were censored. In place of this outcome measure, the percentage of participants who died during the study are provided in the Post-Hoc Analysis Outcome Measure: Percentage of Participants Who Died During the Study.
Time frame: Baseline to date of death from any cause, 12 weeks up to 31 months
Population: Randomized and treated population includes all randomized patients. Patients are analyzed according to the treatment they actually received (ITT population). Median overall survival could not be estimated as most participants were living at the end of the study.
Post Hoc
Percentage of Participants Who Died During the Study
This outcome measure takes the place of the outcome measure for Overall Survival, which could not be reported since the median value could not be calculated.
Time frame: Baseline up to 31 months
Population: Randomized and treated population includes all randomized patients. Patients are analyzed according to the treatment they actually received (ITT population). 25 participants from each treatment group were censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed/Cisplatin/Gefitinib | Percentage of Participants Who Died During the Study | 35.9 Percentage of Participants |
| Pemetrexed/Cisplatin | Percentage of Participants Who Died During the Study | 19.4 Percentage of Participants |