Small Cell Lung Cancer
Conditions
Brief summary
Primary Objective: To demonstrate progression free survival (PFS) improvement for cabazitaxel compared to topotecan in participants with sensitive or resistant/refractory small cell lung cancer following a first line platinum based chemotherapy. Secondary Objectives: * To assess disease progression free rate at 12 weeks * To assess Response Rate (Response Evaluation Criteria in Solid Tumor \[RECIST\] 1.1) and duration of response * To assess Overall Survival (OS) * To assess the Safety (National Cancer Institute - Common Toxicity Criteria \[NCI-CTC\] version 4.03) * To assess the Health-Related Quality of Life (HRQoL)
Detailed description
Participants are to be treated until progressive disease, unacceptable toxicity or refusal for further study treatment. All participants are to be followed for disease progression documentation and for participant status until the study cut-off date.
Interventions
DRUGCabazitaxel
Cabazitaxel 25 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
DRUGTopotecan
Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent.
Sponsors
Sanofi
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
: * Histological/cytological proven locally advanced or metastatic small cell lung cancer with progressive disease during or after first line platinum based chemotherapy * Male or female greater than or equal to (\>=) 18 years (or country's legal age of majority if greater than \[\>\]18 years) * Participants with measurable disease, Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 1
Exclusion criteria
* Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent form prior to enrollment into the study * More than one prior chemotherapy regimen. Prior treatment with topotecan or taxanes * Less than 28 days elapsed from prior treatment with chemotherapy, radiotherapy or surgery to the time of randomization (Radiotherapy for bone pain palliation is allowed) * Adverse events (excluding alopecia) from any prior anticancer therapy of grade \>1 (National Cancer Institute Common Terminology Criteria \[NCI CTCAE\] v4.03) at the time of randomization * Uncontrolled Central Nervous System (CNS) metastases: participants with CNS metastases may have previous irradiation, only participants with stable disease or response to irradiation who are without CNS symptoms and on a maximum steroid dose of dexamethasone 8 mg daily or equivalent could be included * Participants with known leptomeningeal metastases * History of other, invasive neoplasm requiring ongoing therapy * Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization * Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure, stroke or transient ischemic attack * Any severe acute or chronic medical condition, which could impair the ability of the participant to participate in the study or interfere with interpretation of study results * Known Human Immunodeficiency Virus (HIV) disease, or active hepatitis B or C (systematic testing was not required) * Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization * Participant with reproductive potential (M/F) who did not agree to use an accepted and effective method of contraception during the study treatment period and for at least 6 months after the completion of the study treatment. The definition of effective method of contraception was based on the investigator's judgment. Effective method of contraception should also be adapted to local regulation * History of hypersensitivity to polysorbate 80 * Inadequate organ and bone marrow function as evidenced by: * Hemoglobin less than \[\<\] 9.0 gram per deciliter (g/dL) * Absolute neutrophil count \<1.5 x 10\^9 per liter * Platelet count \<100 x 10\^9 per liter * Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and/or alanine aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) \>2.5 x Upper Limit of Normal (ULN) * Alkaline Phosphatase (AP) \>2.5 x ULN. In case of liver metastases AP \>5 x ULN * Total bilirubin \>1.0 x ULN * Serum Creatinine \>1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to Chronic Kidney Disease Epidemiology Collaboration formula, and creatinine clearance \<60 milliliter per minute (mL/min) was exclude the participant. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Randomization to first tumor progression/clinical deterioration or death (maximum 7.6 months) | PFS was defined as the time interval from the date of randomization to the date of occurrence of the first documented tumor progression or death due to any cause, whichever came first. Median PFS was estimated using the Kaplan-Meier method. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization to date of death (maximum 15 months) | Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the last date the participant was known to be alive. Median time was estimated by Kaplan-Meier curve. |
| Progression Free Rate at Week 12 | Week 12 | Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. 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. Death due to disease progression within 12 weeks without radiological documentation of progressive disease was counted as an event. Percentage of participants who were progression free at week 12 are reported. |
| Overall Objective Tumor Response Rate | Randomization to disease progression/occurrence (maximum 7.6 months) | Overall objective tumor response was defined as the proportion of participants with confirmed RECIST 1.1 achieving a complete response (CR) or partial response (PR). CR was defined as disappearance of all target/non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants with overall objective tumor response is reported. |
Countries
Brazil, Canada, Chile, France, Germany, Greece, Hungary, Italy, Norway, Poland, Romania, Russia, South Korea, Spain, Ukraine, United States
Participant flow
Pre-assignment details
A total of 232 participants were screened of which 53 were screen failure and 179 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Cabazitaxel Cabazitaxel 25 mg/m\^2 IV on Day 1 every 3 weeks (21-day cycle) until unacceptable toxicity, disease progression or withdrawal consent. | 90 |
| Topotecan Topotecan 1.5 mg/m\^2 IV on Day 1 to Day 5 every 3 weeks (21-Day cycle) until unacceptable toxicity, disease progression or withdrawal consent. | 89 |
| Total | 179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 4 | 8 |
| Overall Study | Randomized But Not Treated | 1 | 1 |
Baseline characteristics
| Characteristic | Topotecan | Total | Cabazitaxel |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 10 | 60.7 years STANDARD_DEVIATION 9.7 | 59.9 years STANDARD_DEVIATION 9.4 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 17 participants | 48 participants | 31 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 71 participants | 130 participants | 59 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 1 participants | 1 participants | 0 participants |
| Number of Organs Involved | 3.8 organs STANDARD_DEVIATION 1.4 | 3.7 organs STANDARD_DEVIATION 1.3 | 3.6 organs STANDARD_DEVIATION 1.3 |
| Primary Tumor Site Left Lung | 26 participants | 66 participants | 40 participants |
| Primary Tumor Site Lungs | 20 participants | 36 participants | 16 participants |
| Primary Tumor Site Other: Mediastino-Hilar | 0 participants | 1 participants | 1 participants |
| Primary Tumor Site Right Lung | 43 participants | 76 participants | 33 participants |
| Race/Ethnicity, Customized Ethnicity: Hispanic | 3 participants | 7 participants | 4 participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic | 86 participants | 172 participants | 86 participants |
| Race/Ethnicity, Customized Race: Asian/Oriental | 4 participants | 13 participants | 9 participants |
| Race/Ethnicity, Customized Race: Black | 2 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Race: Caucasian/White | 82 participants | 162 participants | 80 participants |
| Race/Ethnicity, Customized Race: Other | 1 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 27 Participants | 54 Participants | 27 Participants |
| Sex: Female, Male Male | 62 Participants | 125 Participants | 63 Participants |
| Stage at Diagnosis IIA | 1 participants | 2 participants | 1 participants |
| Stage at Diagnosis IIB | 1 participants | 3 participants | 2 participants |
| Stage at Diagnosis IIIA | 12 participants | 14 participants | 2 participants |
| Stage at Diagnosis IIIB | 15 participants | 40 participants | 25 participants |
| Stage at Diagnosis IV | 55 participants | 112 participants | 57 participants |
| Stage at Diagnosis Unknown | 5 participants | 8 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 89 | 75 / 88 |
| serious Total, serious adverse events | 36 / 89 | 41 / 88 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS was defined as the time interval from the date of randomization to the date of occurrence of the first documented tumor progression or death due to any cause, whichever came first. Median PFS was estimated using the Kaplan-Meier method. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression.
Time frame: Randomization to first tumor progression/clinical deterioration or death (maximum 7.6 months)
Population: Intent-to-treat (ITT) population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabazitaxel | Progression Free Survival (PFS) | 1.4 months |
| Topotecan | Progression Free Survival (PFS) | 3.0 months |
p-value: <0.000195% CI: [1.563, 3.01]Stratified Two-Sided Log-Rank Test
Secondary
Overall Objective Tumor Response Rate
Overall objective tumor response was defined as the proportion of participants with confirmed RECIST 1.1 achieving a complete response (CR) or partial response (PR). CR was defined as disappearance of all target/non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants with overall objective tumor response is reported.
Time frame: Randomization to disease progression/occurrence (maximum 7.6 months)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabazitaxel | Overall Objective Tumor Response Rate | 0 percentage of participants |
| Topotecan | Overall Objective Tumor Response Rate | 10.1 percentage of participants |
Secondary
Overall Survival
Overall survival was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the last date the participant was known to be alive. Median time was estimated by Kaplan-Meier curve.
Time frame: From randomization to date of death (maximum 15 months)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabazitaxel | Overall Survival | 5.2 months |
| Topotecan | Overall Survival | 6.8 months |
Secondary
Progression Free Rate at Week 12
Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or unequivocal progression of existing non-target lesion. 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. Death due to disease progression within 12 weeks without radiological documentation of progressive disease was counted as an event. Percentage of participants who were progression free at week 12 are reported.
Time frame: Week 12
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabazitaxel | Progression Free Rate at Week 12 | 18.9 percentage of participants |
| Topotecan | Progression Free Rate at Week 12 | 52.8 percentage of participants |