Combination Study Of CP-751,871 With Paclitaxel And Carboplatin In Advanced Lung Cancer

Study Overview
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Brief Summary
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Phase 1b Dose Excalation/Expansion: Identify and characterize safety and tolerability of recommended phase 2 dose of CP-751,871 when administered with paclitaxel and carboplatin Phase 1b Erlotinib Extension: To characterize the safety and tolerability of CP751,871 when administered with paclitaxel, carboplatin and erlotinib. Phase 2: To test the efficacy of CP-751,871 combined with paclitaxel and carboplatin in the treatment of advanced non-small cell lung cancer

Official Title
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A Phase 1b Dose Escalation/Phase 2 Randomized, Non-Comparative, Multiple Center, Open Label Study Of CP 751,871 In Combination With Paclitaxel And Carboplatin And Of Paclitaxel And Carboplatin Alone As First Line Treatment For Advanced Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: CP-751,871
* Drug: paclitaxel
* Drug: carboplatin
* Drug: CP-751,871
* Drug: paclitaxel
* Drug: carboplatin
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced/metastatic lung cancer Exclusion Criteria: Previous treatment with chemotherapy Uncontrolled diabetes History/active cardiovascular disease

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: Phase 2 (Arms A & B)<br>CP-751,871 + paclitaxel + carboplatin | Drug: CP-751,871<br>* Phase 2 Arm A: CP-751,871 20 mg/kg IV over 2.5 hours up to 17 cycles<br>Drug: paclitaxel<br>* Phase 2 Arm A: Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles Phase 2 Arm B: Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles<br>Drug: carboplatin<br>* Phase 2 Arm A: Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles Phase 2 Arm B: Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles<br>|
| Experimental: Phase 1b<br>Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib | Drug: CP-751,871<br>* Phase 1b Dose Escalation/Expansion: CP-751,871 20 mg/kg IV over 2.5 hours (up to 17 cycles) Phase 1b Erlotinib Extension: CP-751,871 20 mg/kg IV over 2.5 hours (up to 17 cycles)<br>Drug: paclitaxel<br>* Phase 1b Dose Escalation/Expansion: paclitaxel 200 mg/m2, IV over 3 hours (up to 6 cycles) Phase 1b Erlotinib Extension: paclitaxel 200 mg/m2, IV over 3 hours (up to 6 cycles)<br>Drug: carboplatin<br>* Phase 1b Dose Escalation/Expansion: carboplatin AUC 6, IV over 15-60 minutes (up to 6 cycles) Phase 1b Erlotinib Extension: carboplatin AUC 6, IV over 15-60 minutes (up to 6 cycles)<br>Drug: erlotinib<br>* Phase 1b Erlotinib Extension: erlotinib 150 mg/day orally every day (up to 17 cycles)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b | The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity. | Start of treatment (baseline) up to the end of Cycle 1 (Day 21) | 
| Recommended Phase 2 Dose (RP2D): Phase 1b |  | Start of treatment (baseline) up to the end of Cycle 1 (Day 21) | 
| Objective Response Rate: Phase 2 | Percentage 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 Tumor (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. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization | 
| Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2 | Percentage 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 Tumor (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. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate: Phase 1b | Percentage 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 Tumor (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. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization | 
| Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b | HAHA are indicators of immunogenicity to CP-751,871. | Day 1 pre-infusion of each cycle up to Cycle 17 (each cycle was 21 day), 150 days after the last CP-751,871 infusion, and last follow up visit (one year post last study dose) | 
| Number of Circulating Endothelial Cells (CECs): Phase 1b |  | Day 1 pre-dose and Days 15 to 21 of Cycle 4 | 
| Number of Circulating Tumor-Related Cells (CTCs) and CTC Insulin-Like Growth Factor 1 Receptor (IGF-IR) Expression: Phase 1b | Blood samples were collected to enumerate the number of total CTCs and CTC insulin-like growth factor 1 receptor (IGF-IR) expression | Day 1 pre-dose and Days 15 to 21 of Cycle 4 | 
| Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b |  | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b |  | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) | 
| Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b | AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b | AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) | 
| Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time. | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) | 
| CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | Concentration at 504 hours post dose | Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | Concentration at 504 hours post dose | Cycle 5 pre-infusion (which is the end of Cycle 4) | 
| Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | Accumulation ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1). Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) | 
| Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | Maximum Observed Plasma Concentration | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) | 
| Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | Maximum Observed Plasma Concentration | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is then end of Cycle 4) | 
| Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 | HAHA are indicators of immunogenicity to CP-751,871 | Day 1 pre-infusion of each Cycle (each cycle was 21 day) up to Cycle 17 and 150 days after the last CP-751,871 infusion | 
| M.D. Anderson Symptom Assessment Inventory (MDASI) in Phase 2 | The MDASI is a 19-item questionnaire that assesses the severity of 13 symptoms over the past 24 hours, as well as how much the symptoms interfered with 6 areas of function (eg, walking, work, mood), when the symptom was at its worst. Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was as bad as you can imagine or interfered completely with their life. Total average score range: 0 to 10. | Day 1 pre-dose of Cycle 1, weekly for Cycle 1 and 2, monthly prior to each subsequent cycle (Cycle 3 up to Cycle 17, each cycle was 21 day), and follow up (one year post last study dose) | 
| The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC-QLQ-C30/-LC13) in Phase 2 | The QLQ-C30/-LC13 is a 43 item, self-administered questionnaire designed to assess health outcomes in clinical trials. In addition to global quality of life, the measure assesses 5 functional domains (physical, role, cognitive, emotional and social functioning) and specific symptoms (eg, nausea, pain). Each item is rated on a 1-4 scale with '1' representing not at all and '4' very much. Within domains, items are scored to obtain a total score with higher scores representative of poorer HRQoL. Scale score range: 0 to 100. | Day 1 pre-dose of Cycle 1, monthly prior to each cycle (up to 17 cycles, each cycle was 21 day), and follow up (one year post last study dose) | 
| Apparent Volume of CP-751,871 Distribution (Vd) for Cycle 4 in Phase 2 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) | 
| Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2 | Systemic clearance. | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). | 
| Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 2 | AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). | 
| CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 2 | Concentration at 504 hours post dose | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). | 
| Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2 | Maximum Observed Plasma Concentration | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). | 
| Progression-Free Survival (PFS): Phase 2 | Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]). | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization | 
| Time to Progression (TTP) in Phase 2 | Time in months from start of study treatment to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]). | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization | 
| Duration of Response (DR) in Phase 2 | Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, chemotherapy, figitumumab, insulin-like growth 1 factor receptor, IGF-IR, monoclonal antibody