Extensive Stage Small Cell Lung Carcinoma
Conditions
Keywords
Cancer, Lung, Metastasis
Brief summary
The purpose of this trial is to compare the progression free survival of LY2510924 + carboplatin + etoposide therapy versus carboplatin + etoposide therapy in participants with extensive-stage disease small cell lung cancer (SCLC)
Interventions
DRUGCarboplatin
Administered intravenously
DRUGEtoposide
Administered intravenously
DRUGLY2510924
Administered subcutaneous injection
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
* histologically or cytologically confirmed extensive-stage disease small cell lung carcinoma * measurable disease as defined by the New Response Evaluation Criteria in Solid Tumors (RECIST): Revised RECIST Guideline (version 1.1) * no prior systemic chemotherapy, immunotherapy, biological, hormonal, or investigational therapy for SCLC * a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale * adequate organ function, including: * hematologic: absolute neutrophil (segmented and bands) count (ANC) greater than or equal to (≥)1.5 x 10\^9/ liter (L), platelets ≥100 x 10\^9/L, and hemoglobin ≥9 grams per deciliter (g/dL). * hepatic: bilirubin less than or equal to (≤)1.5 times upper limits of normal (ULN), and alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 times ULN (AP, AST, and ALT ≤5 times ULN is acceptable if liver has tumor involvement * renal: calculated creatinine clearance (CrCl) ≥45 milliliters per minute (mL/min) based on the standard Cockcroft and Gault formula * For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation), post-menopausal (at least 12 consecutive months of amenorrhea), or compliant with a medically approved contraceptive regimen (intrauterine device \[IUD\], birth control pills, or barrier device) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period. * estimated life expectancy of at least 12 weeks * written informed consent prior to any study-specific procedures * able and willing to learn to self-administer LY2510924, or have a caregiver who is willing to learn and able to administer LY2510924 by subcutaneous (SC) injection
Exclusion criteria
* currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * prior treatment with carboplatin/etoposide or LY2510924 * any concurrent administration of any other antitumor therapy * diagnosis of non-small cell lung cancer (NSCLC) or mixed NSCLC and small cell lung cancer (SCLC) * no prior malignancy other than SCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Participants with a history of low grade (Gleason score ≤6) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry * serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the study requirements * active or ongoing infection during screening requiring the use of systemic antibiotics * serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease as defined by the New York Heart Association Class III or IV * clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously- treated central nervous system (CNS) metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug. * known or suspected allergy to any agent given in association with this trial * pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Randomization to Measured Progressive Disease or Date of Death from Any Cause (Up To 59 Months) | PFS is defined as the time from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For participants who are still alive at the time of analysis and without evidence of tumor progression, PFS will be censored at the date of the most recent objective progression-free observation. For participants who receive subsequent anticancer therapy (except PCI) prior to objective disease progression or death, PFS will be censored at the date of the last objective progression-free observation prior to the date of subsequent therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) | Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause (Up to 59 Months) | ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression. |
| Overall Survival (OS) | Randomization to Date of Death from Any Cause (Up To 59 Months) | Overall survival (OS) is defined as the time from the randomization to the date of death from any cause. For participants who are still alive as of the data cutoff date, OS time will be censored on the date of the participant's last contact (last contact for participants in postdiscontinuation is last known alive date in mortality status). |
| Duration of Overall Response (DOR) | Date of Response to Date of Progressive Disease (Up To 59 Months) | DOR 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. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. |
Countries
United States
Participant flow
Pre-assignment details
Participants who died (any cause) or had disease progression were considered to be study completers.
Participants by arm
| Arm | Count |
|---|---|
| LY2510924 + Carboplatin + Etoposide LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles. | 47 |
| Carboplatin + Etoposide Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles. | 43 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | LY2510924 + Carboplatin + Etoposide | Total | Carboplatin + Etoposide |
|---|---|---|---|
| Age, Continuous | 63.69 years STANDARD_DEVIATION 9.033 | 65.31 years STANDARD_DEVIATION 8.82 | 67.07 years STANDARD_DEVIATION 8.328 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 85 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 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 | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 43 Participants | 83 Participants | 40 Participants |
| Region of Enrollment United States | 47 Participants | 90 Participants | 43 Participants |
| Sex: Female, Male Female | 25 Participants | 51 Participants | 26 Participants |
| Sex: Female, Male Male | 22 Participants | 39 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 47 / 47 | 43 / 43 |
| serious Total, serious adverse events | 24 / 47 | 13 / 43 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is defined as the time from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For participants who are still alive at the time of analysis and without evidence of tumor progression, PFS will be censored at the date of the most recent objective progression-free observation. For participants who receive subsequent anticancer therapy (except PCI) prior to objective disease progression or death, PFS will be censored at the date of the last objective progression-free observation prior to the date of subsequent therapy.
Time frame: Randomization to Measured Progressive Disease or Date of Death from Any Cause (Up To 59 Months)
Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation.The number of participants censored were LY2510924 + Carboplatin + Etoposide=13 and Carboplatin + Etoposide=7.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2510924 + Carboplatin + Etoposide | Progression Free Survival (PFS) | 5.88 Months |
| Carboplatin + Etoposide | Progression Free Survival (PFS) | 5.85 Months |
p-value: 0.807295% CI: [0.6598, 1.7055]Logrank Test
Secondary
Duration of Overall Response (DOR)
DOR 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. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time frame: Date of Response to Date of Progressive Disease (Up To 59 Months)
Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation. The number of participants censored were LY2510924 + Carboplatin + Etoposide=47 and Carboplatin + Etoposide=42.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2510924 + Carboplatin + Etoposide | Duration of Overall Response (DOR) | 4.83 Months |
| Carboplatin + Etoposide | Duration of Overall Response (DOR) | 4.67 Months |
Secondary
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])
ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.
Time frame: Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause (Up to 59 Months)
Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LY2510924 + Carboplatin + Etoposide | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) | 35 Participants |
| Carboplatin + Etoposide | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) | 34 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) is defined as the time from the randomization to the date of death from any cause. For participants who are still alive as of the data cutoff date, OS time will be censored on the date of the participant's last contact (last contact for participants in postdiscontinuation is last known alive date in mortality status).
Time frame: Randomization to Date of Death from Any Cause (Up To 59 Months)
Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation. The numbers of participants censored were LY2510924 + Carboplatin + Etoposide= 4 and Carboplatin + Etoposide=3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2510924 + Carboplatin + Etoposide | Overall Survival (OS) | 9.72 Months |
| Carboplatin + Etoposide | Overall Survival (OS) | 11.14 Months |