Carboplatin And Paclitaxel With Or Without CP-751, 871 (An IGF-1R Inhibitor) For Advanced NSCLC Of Squamous, Large Cell And Adenosquamous Carcinoma Histology

Study Overview
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Brief Summary
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Determine whether the addition of CP- 751,871 in combination with paclitaxel plus carboplatin prolongs survival in patients with locally advanced (Stage IIIB with pleural effusion) or metastatic (Stage IV or recurrent) NSCLC of non adenocarcinoma histology.

Detailed Description
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The study was discontinued on December 29, 2009 due to an analysis by an independent Data Safety Monitoring Committee indicating that the addition of CP-751,871 [figitumumab] to paclitaxel plus carboplatin would be unlikely to meet the primary endpoint of improving overall survival compared to paclitaxel plus carboplatin alone. The DSMC recommendation to terminate the trial was based on futility, not on specific safety concerns; however, the DSMC recommended to investigate hyperglycemia as a potential contributor to the morbidity of the patients.

Official Title
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Randomized, Open Label, Phase III Trial Of CP- 751,871 In Combination With Paclitaxel And Carboplatin Versus Paclitaxel And Carboplatin In Patients With Non Small Cell Lung Cancer

Conditions
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Carcinoma, Squamous Cell, Carcinoma, Adenosquamous, Carcinoma, Large Cell, Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: CP-751,871 (Figitumumab)
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of non small cell lung cancer with a primary histology of predominantly squamous cell, large cell or adenosquamous carcinoma. Advanced NSCLC with documented Stage IIIB (with pleural effusion) or Stage IV or recurrent disease. No prior systemic treatment for NSCLC, except for adjuvant chemotherapy. Adjuvant chemotherapy must have completed for greater than or equal to 12 months prior to randomization. Prior surgery or radiation therapy is permitted if completed at least 3 weeks prior to randomization and all acute toxicities have resolved. ECOG performance status (PS) 0 or 1. Exclusion Criteria: Patients with symptomatic central nervous system (CNS) metastases are not permitted. Patients requiring chronic steroid use or patients with uncontrolled diabetes are not permitted. Patients with other active cancer types are not permitted.

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: A<br>Patients in Arm A will receive CP-751, 871 in combination with paclitaxel and carboplatin intravenously every 21 days for up to six cycles.' | Drug: CP-751,871 (Figitumumab)<br>* CP 751,871 is a potent and selective fully human monoclonal antibody against the insulin like growth factor 1 receptor (IGF-1R). Patients in Arm A will receive CP-751, 871 intravenously every 21 days for up to six cycles.<br>Drug: Carboplatin<br>* Carboplatin is a standard chemotherapeutic agent used in patients with lung cancer. Patients in Arm A will receive carboplatin intravenously every 21 days for up to six cycles.<br>Drug: Paclitaxel<br>* Paclitaxel is a standard chemotherapeutic agent used in patients with lung cancer. Patients in Arm A will receive paclitaxel intravenously every 21 days for up to six cycles.<br>|
| Active Comparator: B<br>Patient in Arm B will receive paclitaxel and carboplatin intravenously every 21 days for up to six cycles. | Drug: Carboplatin<br>* Carboplatin is a standard chemotherapeutic agent used in patients with lung cancer. Patient in Arm B will receive carboplatin intravenously every 21 days for up to six cycles.<br>Drug: Paclitaxel<br>* Paclitaxel is a standard chemotherapeutic agent used in patients with lung cancer. Patient in Arm B will receive paclitaxel intravenously every 21 days for up to six cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact. | Baseline until death, assessed monthly after end of treatment, up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the time from randomization to first progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, with baseline and >=1 on-study assessment, were censored at last disease assessment verifying lack of progression. Progression was determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (20% increase in the sum of target lesions' longest diameter over nadir, unequivocal progression of non-target disease, or appearance of new lesions). | At baseline, every 6 weeks until radiological disease progression or the participant begins a subsequent anticancer therapy, up to 22.7 months. | 
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response(PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as complete disappearance of all target lesions and non-target disease. No new lesons. PR defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions. | At baseline, every 6 weeks until radiological disease progression has been documented or the participant begins a subsequent anticancer therapy, up to 22.7 months | 
| European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. | Day 1 of every cycle (3-week cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months | 
| European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score | QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. | Day 1 of every cycle (3-week cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months | 
| Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range of -0.594 to 1; higher score indicates a better health state. | Day 1 of every cycle (3-weeks cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months | 
| Maximum Observed Plasma Concentration (Cmax) for Figitumumab |  | Cycle 1, Day 1 (predose and 1 hour after end of infusion); Day 1 of Cycles 2, 4, 6 (predose); Cycle 5 Day 1 (predose, 1 hour after end of infusion); 28 days and 150 days after the last figi dose | 
| Minimum Observed Plasma Trough Concentration (Cmin)for Figitumumab |  | Cycle 1, Day 1 (predose and 1 hour after end of infusion); Day 1 of Cycles 2, 4, 6 (predose); Cycle 5 Day 1 (predose, 1 hour after end of infusion); 28 days and 150 days after the last figi dose | 
| Number of Participants With Total Anti-drug Antibodies (ADA) | ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64. | Cycles 1, 2, and 4 (predose); 28 days and 150 days after the last figi dose | 
| Change From Baseline in Serum Insulin Growth Factor 1 (IGF1) Levels |  | Cycles 1 and 4 (predose) and at end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IGF-1R inhibitor, Non-small-cell lung carcinoma, CP-751, 871