Small Cell Lung Cancer
Conditions
Brief summary
This study is a Phase 3, global, multi-center, open-label study of patients with extensive-stage small cell lung cancer. Eligible patients will be randomly assigned to receive either pemetrexed plus carboplatin or etoposide plus carboplatin. It is anticipated that pemetrexed plus carboplatin will offer similar survival benefits as compared to etoposide plus carboplatin.
Interventions
DRUGpemetrexed
500 mg/m2, intravenous (IV), every 21 days x 6 cycles
DRUGetoposide
100 mg/m2, intravenous (IV), days 1-3 x 6 cycles
DRUGcarboplatin
Area under the curve (AUC) 5, intravenous (IV), every 21 days x 6 cycles
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
* Clinical diagnosis of extensive stage small cell lung cancer (SCLC) * Capable of self-care but may be unable to carry out any work activities. * No prior anticancer therapy for SCLC
Exclusion criteria
* have previously participated in a study involving pemetrexed * have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | baseline to date of death from any cause (up to 19.6 months) | Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (Subgroups) | baseline to date of death from any cause (up to 19.6 months) | The effects of individual baseline factors (sex, race, Eastern Cooperative Oncology Group (ECOG) performance, region, lactate dehydrogenase (LDH), age, number of metastatic sites, and history of brain metastases) on overall survival are reported. For two subgroups - LDH\<=upper limit of normal and brain metastases=yes, the upper limits of the 95% confidence interval were not calculable for the etoposide+carboplatin group - instead the number of participants in these two subgroups are presented as a post-hoc outcome measure. |
| Progression Free Survival | baseline to measured progressive disease (up to 14.7 months) | The period from study entry until disease progression, death or date of last contact. |
| Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | baseline and 6 cycles (21-day cycles) | FACT-L measures following domains of health-related quality of life (HR-QL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of lung cancer. Total scores range from 0 to 136, with higher scores representing better HR-QL. A clinically meaningful change is considered to be 5 points. |
| Overall Survival (Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes) | baseline to date of death due to any cause (up to 19.6 months) | The effects of individual baseline factors (lactate dehydrogenase (LDH) and history of brain metastases) on overall survival are reported. The Upper Limits of the 95% Confidence Intervals were not calculable for these factors in the Etoposide+Carboplatin group. The number of participants in these subgroup are instead presented as a Post-Hoc Outcome Measure. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, China, France, Germany, Greece, Hungary, India, Italy, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Participants who received at least one dose of study drug were, per protocol, the patient population used for the summary of safety data (eg, Serious Adverse Events).
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed + Carboplatin Pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 6 cycles Carboplatin: Area under the curve (AUC) 5, intravenous (IV), every 21 days x 6 cycles | 453 |
| Etoposide + Carboplatin Etoposide: 100 mg/m2, intravenous (IV), days 1-3 x 6 cycles Carboplatin: Area under the curve (AUC) 5, intravenous (IV), every 21 days x 6 cycles | 455 |
| Total | 908 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 24 | 15 |
| Overall Study | Death | 32 | 29 |
| Overall Study | Entry Criteria Not Met | 11 | 10 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Physician Decision | 18 | 35 |
| Overall Study | Progressive Disease | 196 | 107 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Sponsor Decision | 67 | 31 |
| Overall Study | Withdrawal by Subject | 9 | 15 |
Baseline characteristics
| Characteristic | Etoposide + Carboplatin | Pemetrexed + Carboplatin | Total |
|---|---|---|---|
| Age, Customized <=65 years | 275 participants | 267 participants | 542 participants |
| Age, Customized >65 years | 180 participants | 186 participants | 366 participants |
| Eastern Cooperative Oncology Group Performance Status 0 - Fully Active | 121 participants | 133 participants | 254 participants |
| Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 277 participants | 265 participants | 542 participants |
| Eastern Cooperative Oncology Group Performance Status 2 - Ambulatory, No Work Activities | 55 participants | 54 participants | 109 participants |
| Eastern Cooperative Oncology Group Performance Status 3 - Partially Confined to Bed, Limited Self Care | 0 participants | 1 participants | 1 participants |
| Eastern Cooperative Oncology Group Performance Status Not Reported | 2 participants | 0 participants | 2 participants |
| History of Brain Metastases No | 412 participants | 410 participants | 822 participants |
| History of Brain Metastases Not Reported | 2 participants | 0 participants | 2 participants |
| History of Brain Metastases Yes | 41 participants | 43 participants | 84 participants |
| Race/Ethnicity Aboriginal and/or Torres Strait Islander | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity African | 8 participants | 5 participants | 13 participants |
| Race/Ethnicity Caucasian | 379 participants | 391 participants | 770 participants |
| Race/Ethnicity East Asian | 49 participants | 43 participants | 92 participants |
| Race/Ethnicity Hispanic | 5 participants | 1 participants | 6 participants |
| Race/Ethnicity Native American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity West Asian | 12 participants | 12 participants | 24 participants |
| Region of Enrollment Argentina | 6 participants | 2 participants | 8 participants |
| Region of Enrollment Australia | 19 participants | 21 participants | 40 participants |
| Region of Enrollment Austria | 14 participants | 5 participants | 19 participants |
| Region of Enrollment Belgium | 17 participants | 12 participants | 29 participants |
| Region of Enrollment Brazil | 7 participants | 4 participants | 11 participants |
| Region of Enrollment China | 18 participants | 14 participants | 32 participants |
| Region of Enrollment France | 10 participants | 19 participants | 29 participants |
| Region of Enrollment Germany | 59 participants | 58 participants | 117 participants |
| Region of Enrollment Greece | 8 participants | 7 participants | 15 participants |
| Region of Enrollment Hungary | 13 participants | 19 participants | 32 participants |
| Region of Enrollment India | 14 participants | 12 participants | 26 participants |
| Region of Enrollment Italy | 8 participants | 7 participants | 15 participants |
| Region of Enrollment Korea, Republic of | 15 participants | 17 participants | 32 participants |
| Region of Enrollment Netherlands | 17 participants | 17 participants | 34 participants |
| Region of Enrollment New Zealand | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Poland | 34 participants | 29 participants | 63 participants |
| Region of Enrollment Portugal | 7 participants | 9 participants | 16 participants |
| Region of Enrollment Romania | 23 participants | 20 participants | 43 participants |
| Region of Enrollment Russian Federation | 16 participants | 30 participants | 46 participants |
| Region of Enrollment South Africa | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Spain | 21 participants | 16 participants | 37 participants |
| Region of Enrollment Taiwan | 12 participants | 11 participants | 23 participants |
| Region of Enrollment Turkey | 13 participants | 15 participants | 28 participants |
| Region of Enrollment United Kingdom | 18 participants | 16 participants | 34 participants |
| Region of Enrollment United States | 83 participants | 92 participants | 175 participants |
| Sex: Female, Male Female | 125 Participants | 128 Participants | 253 Participants |
| Sex: Female, Male Male | 330 Participants | 325 Participants | 655 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 425 / — | 438 / — |
| serious Total, serious adverse events | 150 / — | 134 / — |
Outcome results
Primary
Overall Survival
Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact.
Time frame: baseline to date of death from any cause (up to 19.6 months)
Population: Number of participants with events. In the pemetrexed+carboplatin group, 242 participants were censored. In the etoposide+carboplatin group, 288 participants were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Carboplatin | Overall Survival | 8.1 months |
| Etoposide + Carboplatin | Overall Survival | 10.6 months |
p-value: <0.0195% CI: [1.27, 1.92]Log Rank
Secondary
Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L)
FACT-L measures following domains of health-related quality of life (HR-QL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of lung cancer. Total scores range from 0 to 136, with higher scores representing better HR-QL. A clinically meaningful change is considered to be 5 points.
Time frame: baseline and 6 cycles (21-day cycles)
Population: Number of randomized participants with baseline and non-missing value at respective cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 2 Change from Baseline (n=283, n=310) | 0.17 units on a scale | Standard Deviation 13.72 |
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 4 Change from Baseline (n=199, n=259) | -0.14 units on a scale | Standard Deviation 15.28 |
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 1 Change from Baseline (n=270, n=275) | -0.22 units on a scale | Standard Deviation 12.48 |
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 5 Change from Baseline (n=140, n=203) | 0.27 units on a scale | Standard Deviation 16.34 |
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 3 Change from Baseline (n=225, n=277) | 0.06 units on a scale | Standard Deviation 14.61 |
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 6 Change from Baseline (n=98, n=146) | 0.34 units on a scale | Standard Deviation 17.56 |
| Pemetrexed + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Baseline (n=384, n=383) | 87.42 units on a scale | Standard Deviation 15.4 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 6 Change from Baseline (n=98, n=146) | 3.73 units on a scale | Standard Deviation 14.97 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Baseline (n=384, n=383) | 87.79 units on a scale | Standard Deviation 16.63 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 1 Change from Baseline (n=270, n=275) | 1.55 units on a scale | Standard Deviation 11.11 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 2 Change from Baseline (n=283, n=310) | 1.73 units on a scale | Standard Deviation 12.73 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 3 Change from Baseline (n=225, n=277) | 1.70 units on a scale | Standard Deviation 13.98 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 4 Change from Baseline (n=199, n=259) | 1.69 units on a scale | Standard Deviation 13.42 |
| Etoposide + Carboplatin | Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L) | Cycle 5 Change from Baseline (n=140, n=203) | 1.94 units on a scale | Standard Deviation 14.06 |
Secondary
Overall Survival (Subgroups)
The effects of individual baseline factors (sex, race, Eastern Cooperative Oncology Group (ECOG) performance, region, lactate dehydrogenase (LDH), age, number of metastatic sites, and history of brain metastases) on overall survival are reported. For two subgroups - LDH\<=upper limit of normal and brain metastases=yes, the upper limits of the 95% confidence interval were not calculable for the etoposide+carboplatin group - instead the number of participants in these two subgroups are presented as a post-hoc outcome measure.
Time frame: baseline to date of death from any cause (up to 19.6 months)
Population: Number of randomized participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Region: Intercontinential Region (n=82, n=94) | 7.2 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Sex: Male (n=325, n=330) | 8.2 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Sex: Female (n=128, n=125) | 8.1 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Race: Caucasian (n=391, n=379) | 8.2 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Race: Non-Caucasian (n=62, n=76) | 7.1 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | ECOG: 0 or 1 (n=398, n=398) | 8.5 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | ECOG: 2 (n=54, n=55) | 6.2 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Region: United States (n=92, n=83) | 8.1 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Region: European Union (n=279, n=278) | 8.5 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | LDH: >Upper Limit of Normal (n=276, n=273) | 7.2 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Age: <= 65 years (n=267, n=275) | 8.4 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Age: >65 years (n=186, n=180) | 7.7 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Number Metastatic Sites: <=2 (n=172, n=204) | 10.0 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | Number Metastatic Sites: >=3 (n=273, n=246) | 7.7 months |
| Pemetrexed + Carboplatin | Overall Survival (Subgroups) | History of Brain Metastases: No (n=410, n=412) | 8.2 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Age: >65 years (n=186, n=180) | 9.7 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Region: European Union (n=279, n=278) | 11.2 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Sex: Male (n=325, n=330) | 10.4 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Region: Intercontinential Region (n=82, n=94) | 9.9 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Sex: Female (n=128, n=125) | 11.6 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Number Metastatic Sites: >=3 (n=273, n=246) | 10.3 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Race: Caucasian (n=391, n=379) | 11.2 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | LDH: >Upper Limit of Normal (n=276, n=273) | 9.3 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Race: Non-Caucasian (n=62, n=76) | 8.7 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Number Metastatic Sites: <=2 (n=172, n=204) | 11.5 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | ECOG: 0 or 1 (n=398, n=398) | 11.3 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Age: <= 65 years (n=267, n=275) | 11.5 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | ECOG: 2 (n=54, n=55) | 5.2 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | History of Brain Metastases: No (n=410, n=412) | 10.6 months |
| Etoposide + Carboplatin | Overall Survival (Subgroups) | Region: United States (n=92, n=83) | 11.3 months |
p-value: <0.001Log Rank
p-value: 0.023Log Rank
p-value: <0.001Log Rank
p-value: 0.03Log Rank
p-value: <0.001Log Rank
p-value: 0.519Log Rank
p-value: 0.084Log Rank
p-value: 0.001Log Rank
p-value: 0.003Log Rank
p-value: 0.005Log Rank
p-value: <0.001Log Rank
p-value: 0.013Log Rank
p-value: 0.092Log Rank
p-value: <0.001Log Rank
p-value: <0.001Log Rank
Secondary
Overall Survival (Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes)
The effects of individual baseline factors (lactate dehydrogenase (LDH) and history of brain metastases) on overall survival are reported. The Upper Limits of the 95% Confidence Intervals were not calculable for these factors in the Etoposide+Carboplatin group. The number of participants in these subgroup are instead presented as a Post-Hoc Outcome Measure.
Time frame: baseline to date of death due to any cause (up to 19.6 months)
Population: The upper limit of the 95% Confidence Intervals (CI) were not calculable for these two subgroups in the etoposide+carboplatin group so medians and lower limits of the 95% CI are not presented. A post-hoc outcome measure table provides the number of participants in each subgroup.
Secondary
Progression Free Survival
The period from study entry until disease progression, death or date of last contact.
Time frame: baseline to measured progressive disease (up to 14.7 months)
Population: All randomized participants. Number of participants censored: 113 in Pemetrexed+Carboplatin; 150 in Etoposide+Carboplatin.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Carboplatin | Progression Free Survival | 3.8 months |
| Etoposide + Carboplatin | Progression Free Survival | 5.4 months |
Post Hoc
Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes
Number of participants with Low Density Lipoprotein \<=upper limit of normal and the number of participants with a history of brain metastases. This post-hoc outcome replaces the one for Overall Survival (Subgroups: LDH\<=Upper Limit of Normal and History of Brain Metastases=Yes).
Time frame: baseline to date of death due to any cause (up to 19.6 months)
Population: Number of randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Carboplatin | Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes | LDH: <=Upper Limit of Normal | 167 participants |
| Pemetrexed + Carboplatin | Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes | History of Brain Metastases: Yes | 43 participants |
| Etoposide + Carboplatin | Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes | LDH: <=Upper Limit of Normal | 169 participants |
| Etoposide + Carboplatin | Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes | History of Brain Metastases: Yes | 41 participants |