Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
non-small cell lung cancer, chemotherapy, figitumumab, insulin-like growth 1 factor receptor, IGF-IR, monoclonal antibody
Brief summary
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
Interventions
DRUGCP-751,871
Phase 2 Arm A: CP-751,871 20 mg/kg IV over 2.5 hours up to 17 cycles
DRUGpaclitaxel
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
DRUGcarboplatin
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
DRUGerlotinib
Phase 1b Erlotinib Extension: erlotinib 150 mg/day orally every day (up to 17 cycles)
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
* Diagnosis of advanced/metastatic lung cancer
Exclusion criteria
* Previous treatment with chemotherapy * Uncontrolled diabetes * History/active cardiovascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b | Start of treatment (baseline) up to the end of Cycle 1 (Day 21) | 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. |
| 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 | 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 | 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. |
| Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) | 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) |
| 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 | 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) | 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) |
| Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 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) | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time. |
| Plasma Decay Half-Life (t1/2) of CP-751,871 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 decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Plasma Decay Half-Life (t1/2) of CP-751,871 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) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | Cycle 2 pre-infusion (which is the end of Cycle 1) | Concentration at 504 hours post dose |
| CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | Cycle 5 pre-infusion (which is the end of Cycle 4) | Concentration at 504 hours post dose |
| Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) 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). 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). | Accumulation ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) 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) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) 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 plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Objective Response Rate: Phase 1b | 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 | 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. |
| Maximum Observed Plasma CP-751,871 Concentration (Cmax) 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 then end of Cycle 4) | Maximum Observed Plasma Concentration |
| Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 | 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 | HAHA are indicators of immunogenicity to CP-751,871 |
| M.D. Anderson Symptom Assessment Inventory (MDASI) in Phase 2 | 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 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. |
| The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC-QLQ-C30/-LC13) in Phase 2 | 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) | 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. |
| Apparent Volume of CP-751,871 Distribution (Vd) for Cycle 4 in Phase 2 | 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) | 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. |
| Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2 | 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). | Systemic clearance. |
| 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 | 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). | 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) |
| CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 2 | 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). | Concentration at 504 hours post dose |
| Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2 | 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 Concentration |
| Progression-Free Survival (PFS): Phase 2 | 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 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 \[PD\]). |
| Time to Progression (TTP) in Phase 2 | 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 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 \[PD\]). |
| Duration of Response (DR) in Phase 2 | 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 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. |
| Maximum Observed Plasma CP-751,871 Concentration (Cmax) 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) | Maximum Observed Plasma Concentration |
| Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b | 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) | HAHA are indicators of immunogenicity to CP-751,871. |
| 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 | Day 1 pre-dose and Days 15 to 21 of Cycle 4 | Blood samples were collected to enumerate the number of total CTCs and CTC insulin-like growth factor 1 receptor (IGF-IR) expression |
Countries
Canada, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) Single intravenous (IV) dose of CP-751,871 0.05/0.1/0.8/1.5/3/6/10/20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m\^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter\*minute (mg/mL\*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | 43 |
| CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m\^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter\*minute (mg/mL\*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | 18 |
| CP-751,871 + Paclitaxel + Carboplatin (Phase 2) Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m\^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL\*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | 166 |
| Paclitaxel + Carboplatin (Phase 2) Paclitaxel 200 mg/m\^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL\*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | 55 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1b | Death | 0 | 1 | 2 | 1 | 2 | 2 | 1 | 3 | 9 | 0 | 0 |
| Phase 1b | Lost to Follow-up | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 |
| Phase 1b | Other | 0 | 0 | 2 | 1 | 1 | 1 | 14 | 4 | 4 | 0 | 0 |
| Phase 1b | Randomized but not treated | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Phase 1b | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Phase 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 85 | 31 |
| Phase 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 4 |
| Phase 2 | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 47 | 12 |
| Phase 2 | Randomized but not treated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Phase 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 4 |
Baseline characteristics
| Characteristic | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Total | Paclitaxel + Carboplatin (Phase 2) | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|
| Age, Customized 65 to 69 years old (65 - 69) | 6 participants | 61 participants | 11 participants | 42 participants | 2 participants |
| Age, Customized 70 years old and more than 70 years old (>=70) | 10 participants | 65 participants | 11 participants | 42 participants | 2 participants |
| Age, Customized Less than 65 years old (<65) | 27 participants | 155 participants | 33 participants | 82 participants | 13 participants |
| Age, Customized Unspecified | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Sex/Gender, Customized Female | 18 participants | 96 participants | 21 participants | 49 participants | 8 participants |
| Sex/Gender, Customized Male | 25 participants | 185 participants | 34 participants | 117 participants | 9 participants |
| Sex/Gender, Customized Unspecified | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 2 / 2 | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 17 / 17 | 7 / 7 | 17 / 17 | 162 / 163 | 55 / 56 | 22 / 22 |
| serious Total, serious adverse events | 0 / 3 | 1 / 2 | 2 / 4 | 1 / 3 | 2 / 3 | 2 / 3 | 7 / 17 | 2 / 7 | 9 / 17 | 86 / 163 | 9 / 56 | 3 / 22 |
Outcome results
Primary
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.
Time frame: Start of treatment (baseline) up to the end of Cycle 1 (Day 21)
Population: All participants who received at least one dose of any agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b | NA mg/kg |
Primary
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.
Time frame: 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
Population: All participants who received any of the study treatments. N=number of participants who had measurable disease at baseline and an adequate baseline tumor assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2 | 37.0 percentage of participants |
Comparison: A One-sided p-value for H0: objective response rate \<=0.30 using exact binomial test at level 0.05.p-value: =0.121binomial test
Primary
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.
Time frame: 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
Population: All participants who received any of the study treatments. N=number of participants who had measurable disease at baseline and an adequate baseline tumor assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Objective Response Rate: Phase 2 | 37.4 percentage of participants |
| Paclitaxel + Carboplatin (Phase 2) | Objective Response Rate: Phase 2 | 27.5 percentage of participants |
Comparison: A one-sided p-value for H0: objective response rate \<=0.28 using exact binomial test at level 0.05.p-value: =0.027binomial test
Primary
Recommended Phase 2 Dose (RP2D): Phase 1b
Time frame: Start of treatment (baseline) up to the end of Cycle 1 (Day 21)
Population: All participants who received at least one dose of any agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Recommended Phase 2 Dose (RP2D): Phase 1b | 20 mg/kg |
Secondary
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)
Time frame: 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).
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 3.480 ratio | — |
| Paclitaxel + Carboplatin (Phase 2) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 1.009 ratio | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 1.830 ratio | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 1.550 ratio | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 1.984 ratio | Standard Deviation 0.3015 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 2.260 ratio | — |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b | 1.962 ratio | Standard Deviation 0.4283 |
Secondary
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.
Time frame: 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)
Population: Volume of distribution (Vd) was not calculated based on the status of the program and the limited value this further pharmacokinetic analyses would provide.
Secondary
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.
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel + Carboplatin (Phase 2) | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | 1434 mg.hr/L | Standard Deviation 914.58 |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | 16750 mg.hr/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | 41200 mg.hr/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | 69180 mg.hr/L | Standard Deviation 10651 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | 12100 mg.hr/L | — |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b | 107400 mg.hr/L | Standard Deviation 37604 |
Secondary
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)
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | 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 | 22.30 milligram.hour/Liter (mg.hr/L) | — |
| Paclitaxel + Carboplatin (Phase 2) | 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 | 2011 milligram.hour/Liter (mg.hr/L) | Standard Deviation 1048.6 |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 5320 milligram.hour/Liter (mg.hr/L) | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 12810 milligram.hour/Liter (mg.hr/L) | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 30500 milligram.hour/Liter (mg.hr/L) | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 54650 milligram.hour/Liter (mg.hr/L) | Standard Deviation 14075 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 79820 milligram.hour/Liter (mg.hr/L) | Standard Deviation 21767 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 85240 milligram.hour/Liter (mg.hr/L) | Standard Deviation 33973 |
Secondary
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)
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | 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 | 77.60 mg.hr/L | — |
| Paclitaxel + Carboplatin (Phase 2) | 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 | 2410 mg.hr/L | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 23200 mg.hr/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 52500 mg.hr/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 94360 mg.hr/L | Standard Deviation 11479 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 214000 mg.hr/L | — |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | 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 | 133200 mg.hr/L | Standard Deviation 21292 |
Secondary
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)
Time frame: 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).
Population: AUC504 was not calculated for Cycle 4 in Phase 2 based on the status of the program and the limited value this further PK analyses would provide.
Secondary
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)
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 16.60 mg.hr/L | — |
| Paclitaxel + Carboplatin (Phase 2) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 1235 mg.hr/L | Standard Deviation 713.55 |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 5137 mg.hr/L | Standard Deviation 1682.5 |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 11350 mg.hr/L | Standard Deviation 5551.7 |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 25630 mg.hr/L | Standard Deviation 12536 |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 49260 mg.hr/L | Standard Deviation 18770 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 71200 mg.hr/L | Standard Deviation 26855 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b | 87680 mg.hr/L | Standard Deviation 35247 |
Secondary
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)
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 64.70 mg.hr/L | — |
| Paclitaxel + Carboplatin (Phase 2) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 2255 mg.hr/L | — |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 2670 mg.hr/L | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 23400 mg.hr/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 70300 mg.hr/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 82930 mg.hr/L | Standard Deviation 29539 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 116200 mg.hr/L | Standard Deviation 83683 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b | 114000 mg.hr/L | Standard Deviation 44197 |
Secondary
Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2
Systemic clearance.
Time frame: 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).
Population: Clearance (CL) were not calculated based on the status of the program and the limited value this further PK analyses would provide.
Secondary
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
Time frame: Cycle 2 pre-infusion (which is the end of Cycle 1)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel + Carboplatin (Phase 2) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 0.1610 mg/L | Standard Deviation 0.322 |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 4.550 mg/L | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 9.820 mg/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 28.20 mg/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 61.11 mg/L | Standard Deviation 23.125 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 95.20 mg/L | Standard Deviation 23.354 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b | 86.73 mg/L | Standard Deviation 57.117 |
Secondary
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
Time frame: Cycle 5 pre-infusion (which is the end of Cycle 4)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 0.0000 mg/L | — |
| Paclitaxel + Carboplatin (Phase 2) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 0.4630 mg/L | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 27.70 mg/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 21.20 mg/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 125.3 mg/L | Standard Deviation 16.101 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 357.0 mg/L | — |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b | 158.6 mg/L | Standard Deviation 27.067 |
Secondary
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
Time frame: 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).
Population: C504 was not calculated for Cycle 4 in Phase 2 based on the status of the program and the limited value this further PK analyses would provide.
Secondary
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.
Time frame: 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
Population: Due to the status of the program, duration of response was not analyzed.
Secondary
Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b
Maximum Observed Plasma Concentration
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 1.510 mg/L | — |
| Paclitaxel + Carboplatin (Phase 2) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 17.34 mg/L | Standard Deviation 10.28 |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 38.60 mg/L | Standard Deviation 10.989 |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 75.17 mg/L | Standard Deviation 22.25 |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 147.3 mg/L | Standard Deviation 27.006 |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 275.2 mg/L | Standard Deviation 89.932 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 415.7 mg/L | Standard Deviation 102.14 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b | 483.1 mg/L | Standard Deviation 128.14 |
Secondary
Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b
Maximum Observed Plasma Concentration
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 2.975 mg/L | — |
| Paclitaxel + Carboplatin (Phase 2) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 20.25 mg/L | — |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 40.70 mg/L | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 100.7 mg/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 327.0 mg/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 369.1 mg/L | Standard Deviation 91.602 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 611.3 mg/L | Standard Deviation 43.501 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b | 535.5 mg/L | Standard Deviation 180.97 |
Secondary
Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2
Maximum Observed Plasma Concentration
Time frame: 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).
Population: Cmax was not calculated for Cycle 4 in Phase 2 based on the status of the program and the limited value this further PK analyses would provide.
Secondary
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.
Time frame: 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)
Population: Due to the status of the program, no participants were analyzed for MDASI in phase 2.
Secondary
Number of Circulating Endothelial Cells (CECs): Phase 1b
Time frame: Day 1 pre-dose and Days 15 to 21 of Cycle 4
Population: Per protocol amendment 6, blood samples for the rapid quantification of CECs were no longer collected from participants enrolled in the study. Insufficient data were available to evaluate for correlation.
Secondary
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
Time frame: Day 1 pre-dose and Days 15 to 21 of Cycle 4
Population: Per protocol amendment 6, blood samples for the rapid quantification of CTCs were no longer collected from participants enrolled in the study. Insufficient data were available to evaluate for correlation.
Secondary
Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b
HAHA are indicators of immunogenicity to CP-751,871.
Time frame: 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)
Population: All participants who received at least one dose of any agent. N=number of participants who were analyzed for HAHA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b | 1 number of participants |
| Paclitaxel + Carboplatin (Phase 2) | Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b | 0 number of participants |
Secondary
Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2
HAHA are indicators of immunogenicity to CP-751,871
Time frame: 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
Population: All participants who received any of the study treatments. N=number of participants who were analyzed for HAHA
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 | 0 number of participants |
| Paclitaxel + Carboplatin (Phase 2) | Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 | 0 number of participants |
Secondary
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.
Time frame: 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
Population: All participants who received at least one dose of any agent. N=number of participants who had measurable disease at baseline and an adequate baseline tumor assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Objective Response Rate: Phase 1b | 33.3 percentage of participants |
| Paclitaxel + Carboplatin (Phase 2) | Objective Response Rate: Phase 1b | 25.0 percentage of participants |
Secondary
Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 1.510 milligram/liter (mg/L) | — |
| Paclitaxel + Carboplatin (Phase 2) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 17.34 milligram/liter (mg/L) | Standard Deviation 10.28 |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 37.47 milligram/liter (mg/L) | Standard Deviation 9.0429 |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 75.17 milligram/liter (mg/L) | Standard Deviation 22.25 |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 147.3 milligram/liter (mg/L) | Standard Deviation 27.006 |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 261.3 milligram/liter (mg/L) | Standard Deviation 62.278 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 415.7 milligram/liter (mg/L) | Standard Deviation 102.14 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b | 485.0 milligram/liter (mg/L) | Standard Deviation 131.83 |
Secondary
Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 2.975 mg/L | — |
| Paclitaxel + Carboplatin (Phase 2) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 19.15 mg/L | — |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 40.70 mg/L | — |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 100.7 mg/L | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 327.0 mg/L | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 331.1 mg/L | Standard Deviation 125.77 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 440.3 mg/L | Standard Deviation 211.67 |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b | 447.3 mg/L | Standard Deviation 210.19 |
Secondary
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.
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paclitaxel + Carboplatin (Phase 2) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | 2.84 Day | Standard Deviation 1.82 |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | 10.81 Day | — |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | 8.350 Day | — |
| CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | 9.56 Day | Standard Deviation 2.02 |
| CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | 11.10 Day | — |
| CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b | 9.89 Day | Standard Deviation 1.81 |
Secondary
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.
Time frame: 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)
Population: All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel + Carboplatin (Phase 2) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b | 5.360 Day |
| CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b | 15.40 Day |
Secondary
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 \[PD\]).
Time frame: 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
Population: All participants who received any of the study treatments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | Progression-Free Survival (PFS): Phase 2 | 4.4 months |
| Paclitaxel + Carboplatin (Phase 2) | Progression-Free Survival (PFS): Phase 2 | 4.5 months |
| CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Progression-Free Survival (PFS): Phase 2 | 4.3 months |
| CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | Progression-Free Survival (PFS): Phase 2 | 5.1 months |
Secondary
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.
Time frame: 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)
Population: Due to the status of the program, no participants were analyzed for EORTC-QLQ-C30/-LC13 in phase 2.
Secondary
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 \[PD\]).
Time frame: 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
Population: Due to the status of the program, time to progression was not was not analyzed.