Small Cell Lung Carcinoma
Conditions
Keywords
Small Cell Lung Cancer, Extensive stage disease, SCLC, IGF-1R inhibitor
Brief summary
This study will summarize the safety of patients receiving figitumumab combined with etoposide and cisplatin (or carboplatin) vs. patients receiving etoposide and cisplatin (or carboplatin) alone as first line treatment for extensive stage disease Small Cell Lung Cancer.
Detailed description
The study prematurely discontinued on January 26, 2011 due to slow enrollment. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.
Interventions
DRUGfigitumumab
Figitumumab (20 mg/kg)
Cisplatin (75 mg/m2 IV on Day 1) or Carboplatin AUC 5
DRUGEtoposide
Etoposide (100 mg/m2 IV on Days 1, 2 and 3)
Sponsors
Pfizer
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 confirmed diagnosis of extensive stage disease Small Cell Lung Cancer (SCLC), with tumor biopsy sample required. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Total IGF-1 \> or = 120 ng/ml
Exclusion criteria
* Any prior systemic therapy for Small Cell Lung Cancer (SCLC) * HbA1c \> or = 5.7%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression | Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS time (days) = \[event (progression or death) date or censor date - date of randomization + 1\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Every 3 months until death or 12 months from the date the last participant was randomized | Overall survival was the duration from enrollment to death due to any cause. For participants who are alive, overall survival was censored at the last contact. Survival time (days) = \[death date (last known alive date) - date of randomization +1\]. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to follow-up (90 days post dose) | AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. |
| Maximum Observed Plasma Concentration (Cmax) of Figitumumab | Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose | — |
| Minimum Observed Plasma Trough Concentration (Cmin) of Figitumumab | Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Etoposide | Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Maximum Observed Plasma Concentration (Cmax) of Etoposide | Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion | — |
| Number of Participants With Objective Response | Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. |
| Cancer Dyspnea Scale (CDS) Score | Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression | The Cancer Dyspnea Scale consists of 12 questions that assess 3 domains of dyspnea (sense of effort, anxiety and discomfort) related to lung cancer. The questions are answered on 5-point Likert scale ranging from 1 to 5 (1 Not at All to 5 Very Much). |
| Numeric Rating Scale (NRS) Score | Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression | The Numeric Rating Scale (NRS) is a 1-item self-reported questionnaire designed to assess worst pain severity. Overall scores range from 0 to 10, with low scores representing a lower level of pain. |
| Pre-treatment Levels of Tumor Biomarkers Involved in Insulin-Like Growth Factor 1 (IGF-I) Signaling Pathway | Baseline prior to dosing | — |
| Levels of Serum Circulating Insulin-like Growth Factor (IGF) Pathway Related Markers | Baseline (Cycle 1, Day 1 prior to dosing), Cycle 4 (Day 1), at the end of treatment visit (28 days post last figitumumab dose) | — |
| Number of Total Circulating Tumor-Related Cells (CTCs) and Insulin-Like Growth Factor 1 Receptor (IGF-IR)-Expressing CTCs | Baseline (Cycle 1, Day 1), Cycle 4 (Day 1) and at the end of treatment visit (28 days post last figitumumab dose) | Pre-treatment and post-treatment counts of total and IGF-IR-positive CTCs |
| Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab | Day 2 of Cycle 1 (or Day 1 of the initial cycle starting single agent figitumumab); Day 1 of Cycles 2 and 4; Day 28 and Day 90 post last figitumumab dose | Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab |
Countries
Canada, Hungary, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Figitumumab + Cisplatin or Carboplatin + Etoposide Figitumumab 20 mg/kg administered IV over 1 hour on Day 2 of Cycle 1 and on Day 1 of subsequent cycles (up to 17 cycles in the absence of further disease progression or intolerable toxicity). Cisplatin 75 mg/m\^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL\*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m\^2 IV over 1 hour on Day 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle. | 5 |
| Cisplatin or Carboplatin + Etoposide Cisplatin 75 mg/m\^2 IV over 1 hour or carboplatin at a dose to attain the target AUC of 5 mg/mL\*min IV over 15-60 minutes on Day 1 (up to 6 cycles) followed by etoposide 100 mg/m\^2 IV over 1 hour on Days 1, 2 and 3 of each cycle (up to 6 cycles or until progression or intolerable toxicity). Each cycle was 21 days cycle. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Study terminated | 0 | 2 |
Baseline characteristics
| Characteristic | Figitumumab + Cisplatin or Carboplatin + Etoposide | Cisplatin or Carboplatin + Etoposide | Total |
|---|---|---|---|
| Age Continuous | 60.4 years STANDARD_DEVIATION 4.4 | 53.8 years STANDARD_DEVIATION 11 | 57.4 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 3 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 | 5 / 5 | 4 / 4 |
| serious Total, serious adverse events | 4 / 5 | 2 / 4 |
Outcome results
Primary
Progression-Free Survival (PFS)
Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS time (days) = \[event (progression or death) date or censor date - date of randomization + 1\].
Time frame: Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression
Population: No analysis of progression-free survival was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Etoposide
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion
Population: No analysis of pharmacokinetics (PK) parameters for etoposide was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Cancer Dyspnea Scale (CDS) Score
The Cancer Dyspnea Scale consists of 12 questions that assess 3 domains of dyspnea (sense of effort, anxiety and discomfort) related to lung cancer. The questions are answered on 5-point Likert scale ranging from 1 to 5 (1 Not at All to 5 Very Much).
Time frame: Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression
Population: No analysis for cancer dyspnea scale score was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Levels of Serum Circulating Insulin-like Growth Factor (IGF) Pathway Related Markers
Time frame: Baseline (Cycle 1, Day 1 prior to dosing), Cycle 4 (Day 1), at the end of treatment visit (28 days post last figitumumab dose)
Population: No analysis for serum circulating IGF pathway related markers was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Etoposide
Time frame: Cycles 1 and 2, Day 1 and Day 2 (within 3 hours prior to Day 1 etoposide infusion; 1, 1.5, 2, 3, 6, and 24 hours post Day 1 etoposide infusion); Cycles 4 and 5, Day 2: 24 hours post Day 1 etoposide infusion
Population: No analysis of PK parameters for etoposide was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Figitumumab
Time frame: Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose
Population: No analysis of Cmax for figitumumab was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) of Figitumumab
Time frame: Cycle 1, Day 2; Day 1 of Cycles 2, 4, 5, 6, 10 and 15; Day 28 and Day 90 post last figitumumab dose
Population: No analysis of Cmin for figitumumab was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly or birth defect in the offspring of a study subject.
Time frame: Baseline up to follow-up (90 days post dose)
Population: All randomized participants who received at least one dose of any agent of the combination were included in the safety analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Figitumumab + Cisplatin or Carboplatin + Etoposide | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 5 participants |
| Figitumumab + Cisplatin or Carboplatin + Etoposide | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 4 participants |
| Cisplatin or Carboplatin + Etoposide | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 4 participants |
| Cisplatin or Carboplatin + Etoposide | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 2 participants |
Secondary
Number of Participants With Objective Response
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST.
Time frame: Baseline, every 2nd cycle (between Day 15-21, 1 cycle = 21 days) starting with Cycle 2 until disease progression, at the end of treatment visit (if more than 28 days have passed since last evaluation); and every 6 weeks until disease progression
Population: No analysis of objective response was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Number of Total Circulating Tumor-Related Cells (CTCs) and Insulin-Like Growth Factor 1 Receptor (IGF-IR)-Expressing CTCs
Pre-treatment and post-treatment counts of total and IGF-IR-positive CTCs
Time frame: Baseline (Cycle 1, Day 1), Cycle 4 (Day 1) and at the end of treatment visit (28 days post last figitumumab dose)
Population: No analysis of total CTCs and IGF-IR-expressing CTCs was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Numeric Rating Scale (NRS) Score
The Numeric Rating Scale (NRS) is a 1-item self-reported questionnaire designed to assess worst pain severity. Overall scores range from 0 to 10, with low scores representing a lower level of pain.
Time frame: Day 1 of every cycle (up to 17 cycles), at the end of treatment visit (28 days post last dose); then every 6 weeks until disease progression
Population: No analysis for NRS score was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Overall Survival (OS)
Overall survival was the duration from enrollment to death due to any cause. For participants who are alive, overall survival was censored at the last contact. Survival time (days) = \[death date (last known alive date) - date of randomization +1\].
Time frame: Every 3 months until death or 12 months from the date the last participant was randomized
Population: No analysis of overall survival was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab
Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab
Time frame: Day 2 of Cycle 1 (or Day 1 of the initial cycle starting single agent figitumumab); Day 1 of Cycles 2 and 4; Day 28 and Day 90 post last figitumumab dose
Population: No analysis of ADA response was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.
Secondary
Pre-treatment Levels of Tumor Biomarkers Involved in Insulin-Like Growth Factor 1 (IGF-I) Signaling Pathway
Time frame: Baseline prior to dosing
Population: No analysis of tumor biomarkers was performed as the study was terminated prematurely due to low participants enrollment and the halting of the figitumumab development program. As a result, the only endpoint analyzed for the study was safety and tolerability of figitumumab ± cisplatin (or carboplatin) and etoposide.