A Study Of Cisplatin (Or Carboplatin) And Etoposide With Or Without Figitumumab (CP-751,871) In Patients With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2, Randomized, Open Label Study Of Figitumumab (CP-751,871) Plus Cisplatin (Or Carboplatin) And Etoposide, Versus Cisplatin (Or Carboplatin) And Etoposide Alone, As First Line Treatment In Patients With Extensive Stage Disease Small Cell Lung Cancer

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: figitumumab
* Drug: Cisplatin (Or Carboplatin)
* Drug: Etoposide
* Drug: Cisplatin (Or Carboplatin)
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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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%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Figitumumab (CP-751,871) Plus Chemotherapy [Cisplatin (Or Carboplatin) And Etoposide] All drugs to be administered on a 21 day cycle | Drug: figitumumab<br>* Figitumumab (20 mg/kg)<br>Drug: Cisplatin (Or Carboplatin)<br>* Cisplatin (75 mg/m2 IV on Day 1) or Carboplatin AUC 5<br>Drug: Etoposide<br>* Etoposide (100 mg/m2 IV on Days 1, 2 and 3)<br>|
| Active Comparator: Arm B<br>Chemotherapy [Cisplatin (Or Carboplatin) And Etoposide] All drugs to be administered on a 21 day cycle | Drug: Cisplatin (Or Carboplatin)<br>* Cisplatin (75 mg/m2 IV on Day 1) or Carboplatin AUC 5<br>Drug: Etoposide<br>* Etoposide (100 mg/m2 IV on Days 1, 2 and 3)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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]. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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]. | Every 3 months until death or 12 months from the date the last participant was randomized | 
| 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. | Baseline up to follow-up (90 days post dose) | 
| 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 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 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 | 
| 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 | 
| 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 | 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 | 
| 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). | 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 | 
| 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. | 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 | 
| 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 | Pre-treatment and post-treatment counts of total and IGF-IR-positive CTCs | Baseline (Cycle 1, Day 1), Cycle 4 (Day 1) and at the end of treatment visit (28 days post last figitumumab dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small Cell Lung Cancer, Extensive stage disease, SCLC, IGF-1R inhibitor