Non Small Cell Lung Cancer
Conditions
Brief summary
This is a multicenter, open-label, randomized, two-arm Phase 2 study comparing pemetrexed plus best supportive care with best supportive care alone as maintenance therapy following first-line treatment with a pemetrexed-cisplatin combination in patients with advanced non-squamous non-small cell lung cancer. A total of approximately 100 patients are planned to be enrolled, and following completion of four cycles of pemetrexed-cisplatin (Induction Phase) those patients in which disease progression has not occurred will be randomized in a 2:1 ratio to one of two treatment arms (Maintenance Phase): Arm A (pemetrexed plus best supportive care) or Arm B (best supportive care alone).
Interventions
DRUGpemetrexed
500 mg/m², IV, Day 1 of each 21-day cycle for 6 cycles
DRUGBest Supportive Care
Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.
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
1. You must be at least 18 years old 2. You must have been diagnosed with non-squamous non-small cell lung cancer (NSCLC) 3. You must have had no prior systemic anticancer therapy for lung cancer 4. You must live close enough to the study doctor to be able to visit regularly for follow up 5. You must have signed informed consent form indicating your willingness to take part in this study 6. Your laboratory and medical history and tests must meet study requirements
Exclusion criteria
1. Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry 2. Prior radiotherapy and surgery should be completed at least 4 weeks prior to initiation of treatment 3. Serious concomitant systemic disorder (e.g., active infection including human immunodeficiency virus, or unstable cardiovascular disease) 4. Prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer unless treated at least 5 years previously with no subsequent evidence of recurrence 5. Brain metastasis 6. Presence of clinically significant (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry 7. Significant weight loss (greater than 10%), over the previous 6 weeks before study entry 8. Concurrent administration of any other antitumor therapy 9. Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents such as piroxicam) 10. Inability or unwillingness to take folic acid, dexamethasone (or equivalent) or vitamin B12 supplementation 11. Pregnancy or breast-feeding 12. You are allergic to pemetrexed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival During Maintenance Phase | Randomization to progression of disease (PD) or date of death from any cause up to 30.9 months | Progression free survival is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in maintenance phase uses the last lesion assessment prior to randomization as the baseline assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival During Overall Period (Induction Phase [IP] + Maintenance Phase [MP]) | First dose of study drug during IP to PD or date of death from any cause up to 33.6 months | Progression-free survival in overall period is defined as the time from the date of first dose of study drug during IP until the date of PD or death from any cause. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in overall period uses the screening lesion assessment prior to the induction phase as the baseline assessment. |
| Overall Survival During Maintenance Phase | Randomization to PD or date of death from any cause up to 31.3 months | Overall survival in maintenance phase is defined as the time from randomization to death. Participants who were alive were censored at the last contact. |
| Overall Survival During Overall Period (IP + MP) | First dose of study drug during IP to PD or date of death from any cause up to 34.1 months | Overall survival in overall period is defined as the time from first dose of study drug during IP to death. Participants who were alive were censored at the last contact. |
| Number of Participants With Adverse Events (AEs) During Overall Period | First dose of study drug during IP through overall study completion (up to 34.3) months | The list of serious adverse events (SAEs) and other non-serious adverse events (AEs) are in Adverse Events Section. |
| Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Randomization to measured PD up to 31.4 months | Tumor response rate (%) is the number of responders (participants with best response of CR or PR) divided by the number of participants qualified for tumor response according to RECIST criteria multiplied by 100. Disease control rate is percentage of participants with a best response of stable disease \[SD\], PR, or CR. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; PD is≥20% increase in sum of longest diameter of target lesions. SD= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
Countries
Egypt, Lebanon, Saudi Arabia
Participant flow
Pre-assignment details
Induction phase (IP) is from first dose of study drug until randomization and entering to maintenance phase (MP) or discontinuation from treatment during IP. 106 participants were treated during IP. MP is from randomization to discontinuation from treatment. Overall period is IP+MP, whereas overall study is MP only.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) Pemetrexed: 500 mg/m², IV, Day 1 of each 21-day cycle for 6 cycles
Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician. | 28 |
| Best Supportive Care (Maintenance Phase) Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician. | 27 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Induction Phase | Death | 73 | 0 | 0 |
| Induction Phase | Lost to Follow-up | 10 | 0 | 0 |
| Induction Phase | Physician Decision | 2 | 0 | 0 |
| Induction Phase | Withdrawal by Subject | 2 | 0 | 0 |
| Maintenance Phase | Death | 0 | 17 | 15 |
| Maintenance Phase | Lost to Follow-up | 0 | 5 | 2 |
| Maintenance Phase | Physician Decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Best Supportive Care (Maintenance Phase) | Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Total |
|---|---|---|---|
| Age Continuous | 62.9 years STANDARD_DEVIATION 9.97 | 57.4 years STANDARD_DEVIATION 12.52 | 60.1 years STANDARD_DEVIATION 11.57 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at randomization of maintenance phase 0 - Fully active | 8 participants | 6 participants | 14 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at randomization of maintenance phase 1 - Ambulatory, restricted strenuous activity | 17 participants | 20 participants | 37 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at randomization of maintenance phase 2 - Ambulatory, unable to carry out work activity | 2 participants | 2 participants | 4 participants |
| Lesion Response to induction phase Complete Response (CR) | 1 participants | 0 participants | 1 participants |
| Lesion Response to induction phase Partial Response (PR) | 11 participants | 10 participants | 21 participants |
| Lesion Response to induction phase Stable Disease (SD) | 13 participants | 17 participants | 30 participants |
| Lesion Response to induction phase Unknown | 2 participants | 1 participants | 3 participants |
| Pathological Diagnosis Adenocarcinoma | 21 participants | 19 participants | 40 participants |
| Pathological Diagnosis Large Cells Lung Carcinoma | 5 participants | 8 participants | 13 participants |
| Pathological Diagnosis Mixed Cell Carcinoma, Lung | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized African | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 26 Participants | 26 Participants | 52 Participants |
| Region of Enrollment Egypt | 19 participants | 24 participants | 43 participants |
| Region of Enrollment Lebanon | 7 participants | 4 participants | 11 participants |
| Region of Enrollment Saudi Arabia | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 37 Participants |
| Stage of Disease at The Time of Entry into This Study Stage III B - Locally advanced | 10 participants | 9 participants | 19 participants |
| Stage of Disease at The Time of Entry into This Study Stage IV - Metastasized | 17 participants | 19 participants | 36 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 28 | 16 / 27 | 74 / 106 |
| serious Total, serious adverse events | 1 / 28 | 1 / 27 | 13 / 106 |
Outcome results
Primary
Progression Free Survival During Maintenance Phase
Progression free survival is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in maintenance phase uses the last lesion assessment prior to randomization as the baseline assessment.
Time frame: Randomization to progression of disease (PD) or date of death from any cause up to 30.9 months
Population: Participants who were randomized into maintenance phase and had measurable or evaluable lesions at baseline (last assessment before randomization) and post-baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Progression Free Survival During Maintenance Phase | 3.2 months |
| Best Supportive Care (Maintenance Phase) | Progression Free Survival During Maintenance Phase | 3.2 months |
p-value: 0.181595% CI: [0.42, 1.37]Regression, Cox
Secondary
Number of Participants With Adverse Events (AEs) During Overall Period
The list of serious adverse events (SAEs) and other non-serious adverse events (AEs) are in Adverse Events Section.
Time frame: First dose of study drug during IP through overall study completion (up to 34.3) months
Population: Participants who took at least one dose of study drug during IP, and randomized to maintenance phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Number of Participants With Adverse Events (AEs) During Overall Period | Adverse Events (AE) | 15 participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Number of Participants With Adverse Events (AEs) During Overall Period | Serious Adverse Events (SAE) | 1 participants |
| Best Supportive Care (Maintenance Phase) | Number of Participants With Adverse Events (AEs) During Overall Period | Serious Adverse Events (SAE) | 1 participants |
| Best Supportive Care (Maintenance Phase) | Number of Participants With Adverse Events (AEs) During Overall Period | Adverse Events (AE) | 16 participants |
| Pemetrexed Plus Cisplatin (Induction Phase) | Number of Participants With Adverse Events (AEs) During Overall Period | Serious Adverse Events (SAE) | 13 participants |
| Pemetrexed Plus Cisplatin (Induction Phase) | Number of Participants With Adverse Events (AEs) During Overall Period | Adverse Events (AE) | 74 participants |
Secondary
Overall Survival During Maintenance Phase
Overall survival in maintenance phase is defined as the time from randomization to death. Participants who were alive were censored at the last contact.
Time frame: Randomization to PD or date of death from any cause up to 31.3 months
Population: Participants who were randomized into maintenance phase and had measurable or evaluable lesions at baseline (last assessment before randomization) and post-baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Overall Survival During Maintenance Phase | 12.2 months |
| Best Supportive Care (Maintenance Phase) | Overall Survival During Maintenance Phase | 11.8 months |
p-value: 0.723995% CI: [0.56, 2.28]Regression, Cox
Secondary
Overall Survival During Overall Period (IP + MP)
Overall survival in overall period is defined as the time from first dose of study drug during IP to death. Participants who were alive were censored at the last contact.
Time frame: First dose of study drug during IP to PD or date of death from any cause up to 34.1 months
Population: Participants who took at least one dose of study drug during IP and had measurable or evaluable lesions at baseline (assessment before induction phase) and post baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Overall Survival During Overall Period (IP + MP) | 15.4 months |
| Best Supportive Care (Maintenance Phase) | Overall Survival During Overall Period (IP + MP) | 16.4 months |
p-value: 0.637695% CI: [0.59, 2.38]Regression, Cox
Secondary
Progression Free Survival During Overall Period (Induction Phase [IP] + Maintenance Phase [MP])
Progression-free survival in overall period is defined as the time from the date of first dose of study drug during IP until the date of PD or death from any cause. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in overall period uses the screening lesion assessment prior to the induction phase as the baseline assessment.
Time frame: First dose of study drug during IP to PD or date of death from any cause up to 33.6 months
Population: Participants who took at least one dose of study drug during IP and had measurable or evaluable lesions at baseline (assessment before induction phase) and post baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Progression Free Survival During Overall Period (Induction Phase [IP] + Maintenance Phase [MP]) | 6.2 months |
| Best Supportive Care (Maintenance Phase) | Progression Free Survival During Overall Period (Induction Phase [IP] + Maintenance Phase [MP]) | 6.0 months |
p-value: 0.123395% CI: [0.4, 1.26]Regression, Cox
Secondary
Tumor Response Rate and Disease Control Rate After Induction Phase (IP)
Tumor response rate (%) is the number of responders (participants with best response of CR or PR) divided by the number of participants qualified for tumor response according to RECIST criteria multiplied by 100. Disease control rate is percentage of participants with a best response of stable disease \[SD\], PR, or CR. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; PD is≥20% increase in sum of longest diameter of target lesions. SD= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Randomization to measured PD up to 31.4 months
Population: Participants who were randomized into maintenance phase and had measurable or evaluable lesions at baseline (last assessment before randomization) and post-baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Best Overall Response Rate | 0 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | CR | 0 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | PR | 0 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | SD | 57.1 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Disease Control Rate | 57.1 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | PD | 32.1 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Early Death From Malignant Disease | 7.1 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Early Death From Toxicity | 0 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Early Death From other cause | 3.6 percentage of participants |
| Pemetrexed Plus Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Unknown | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Early Death From Toxicity | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Best Overall Response Rate | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | PD | 37.0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | CR | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Unknown | 18.5 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | PR | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Early Death From Malignant Disease | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | SD | 44.4 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Early Death From other cause | 0 percentage of participants |
| Best Supportive Care (Maintenance Phase) | Tumor Response Rate and Disease Control Rate After Induction Phase (IP) | Disease Control Rate | 44.4 percentage of participants |