Advanced Non-Hematologic Malignancies
Conditions
Keywords
non-hematologic cancer, advanced solid tumors, prostrate cancer
Brief summary
This clinical trial is designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamic effects of escalating doses of CP 751,871 given in combination with docetaxel in patients with non-hematologic malignancies for whom docetaxel is a reasonable treatment option.
Interventions
DRUGCP-751,871
CP-751,871 was given intravenously \[IV\] every 3 weeks in escalating doses ranging from 0.1 mg/kg up to 20 mg/kg. Standard doses of Docetaxel were given every 3 weeks with CP-751,871. Study therapy was continued until disease progression, lack of tolerability for up to 17 cycles (approximately 1 year).
DRUGDocetaxel
Docetaxel up to 75 mg/m\^2 was administered intravenously \[IV\] on Day 1 of each 3-week dosing cycle.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 18 years * Documented advanced-stage non-hematologic malignancy for whom docetaxel monotherapy is a reasonable treatment option * Eastern Cooperative Oncology Group \[ECOG\] performance status 0-1
Exclusion criteria
* Significant active cardiac disease * Chemotherapy, biological or investigational agents within 4 weeks prior to dosing * Inadequate bone marrow, renal, cardiac or liver function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1 | 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4 | 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | — |
| Maximum Tolerated Dose (MTD) | Cycle 1 Day 1 through Cycle 1 Day 21 | — |
| Recommended Phase 2 Dose (RP2D) | Cycle 1 Day 1 through Cycle 1 Day 21 | — |
| Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1 | 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion) |
| Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4 | 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion) |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1 | 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | 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 (AUClast) of Docetaxel in Cycle 4 | 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1 | 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose |
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4 | 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose |
| Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1 | 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | — |
| Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4 | 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | — |
| Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1 | 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Maximum Observed Plasma Concentration (Cmax) divided by dose |
| Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4 | 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion | Maximum Observed Plasma Concentration (Cmax) divided by dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | 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 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | — |
| Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | 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 blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | 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 blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Apparent Volume of Distribution (Vz/F) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | 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. |
| Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | 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 (Vz/F) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | 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. |
| Volume of Distribution (Vz) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | 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. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle. |
| Observed Accumulation Ratio (Rac) of CP-751,871 | 30 minutes prior to CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of CP-751,871 infusion; and 30 minutes prior to the next cycle CP-751,871 infusion (Day 22) in Cycle 1 and Cycle 4 | AUCtao of Cycle 4 divided by AUC(0-d22) of Cycle 1 |
| Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Cycle 1: 30 minutes prior to the Cycle 2 CP-751,871 infusion (this is Day 22 for Cycle 1); Cycle 4: 30 minutes prior to the Cycle 5 CP-751,871 infusion (this is Day 22 for Cycle 4) | Cday22 is the measured CP-751,871 plasma concentration in blood sample collected at Day 22. |
| Time of Last Quantifiable Time Point (Tlast) of CP-751,871 in Cycle 1 and Cycle 4 | Cycle 1 and 4: prior to CP-751,871 infusion, at 1 hour post CP-751,871 infusion, and at 1, 3, 7 days post end of docetaxel infusion | Blood samples were collected at timepoints prespecified in the study protocol. Tlast of CP-751,871 was the last time point when blood sample collected was quantifiable for CP-751,871. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle. |
| Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 30 minutes predose at each cycle, End of Study (28 days after the last CP-751,871 infusion), and 150 days after the last CP-751,871 infusion | The development of HAHA is considered clinically relevant when temporally associated to the onset of adverse events or a significant decrease in the plasma concentrations of CP-751,871. The positive value is defined as ≥3.32. |
| Number of Participants With Objective Response (OR) | Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days) | Number of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to 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 to Tumor Progression (TTP) | Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days) | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]) |
| Circulating Tumor Cells (CTCs), CTCs Expressing Insulin-like Growth Factor 1 Receptor (IGF-1R), and Circulating Endothelial Cells (CECs) | Predose on Day 1 and on Day 8 of each cycle, and End of Study (28 days after the last CP-751,871 infusion) | — |
| Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | — |
| Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | — |
| Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle. |
| Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)(dn)) of CP-751,871 in Cycle 1 | 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22) | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) divided by total dose |
| Dose Normalized Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)(dn)) of CP-751,871 in Cycle 4 | 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22) | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) divided by total dose |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all enrolled participants who received single dose of docetaxel infusion up to 75 mg/m\^2 over 1 hour intravenously and single dose of CP-751,871 infusion 0.1, 0.4, 0.8, 1.5, 3, 6, 10 or 20 mg/kg intravenously at each cycle (1 cycle = 21 days). | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 3 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive disease | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 9 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 59.4 Years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 40 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 9 / 9 | 19 / 19 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 7 / 9 | 11 / 19 |
Outcome results
Primary
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion)
Time frame: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1 | 2852.11 nanogram*hour/millilitre (ng*hr/mL) | Standard Deviation 943.017 |
Primary
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4
Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion)
Time frame: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4 | 2526.19 ng*hr/mL | Standard Deviation 925.815 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1 | 2770.71 ng*hr/mL | Standard Deviation 946.869 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 4 | 2438.34 ng*hr/mL | Standard Deviation 917.884 |
Primary
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose
Time frame: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1 | 36.9428 ng•hr/mL/(mg/m^2) | Standard Deviation 12.6249 |
Primary
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose
Time frame: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4 | 35.16 ng•hr/mL/(mg/m^2) | Standard Deviation 11.1288 |
Primary
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1
Maximum Observed Plasma Concentration (Cmax) divided by dose
Time frame: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1 | 35.4256 ng/mL/(mg/m^2) | Standard Deviation 8.1046 |
Primary
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4
Maximum Observed Plasma Concentration (Cmax) divided by dose
Time frame: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4 | 35.3 ng/mL/(mg/m^2) | Standard Deviation 6.0377 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1
Time frame: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1 | 2656.92 ng/mL | Standard Deviation 607.843 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4
Time frame: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4 | 2430 ng/mL | Standard Deviation 497.343 |
Primary
Maximum Tolerated Dose (MTD)
Time frame: Cycle 1 Day 1 through Cycle 1 Day 21
Population: Safety analysis set: all enrolled participants who started treatment, but excluding those who were enrolled in the expansion cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Maximum Tolerated Dose (MTD) | NA mg/kg |
Primary
Recommended Phase 2 Dose (RP2D)
Time frame: Cycle 1 Day 1 through Cycle 1 Day 21
Population: Safety analysis set: all enrolled participants who started treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Recommended Phase 2 Dose (RP2D) | 20 mg/kg |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1
Time frame: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1 | 0.9179 hr | Standard Deviation 0.1833 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4
Time frame: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Population: Participants who were enrolled into the PK drug interaction expansion cohort, started treatment and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4 | 0.8066 hr | Standard Deviation 0.1296 |
Secondary
Apparent Volume of Distribution (Vz/F) of CP-751,871 in Cycle 1
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: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to registration error: apparent volume of distribution (Vz/F) is for oral dose. Volume of Distribution (Vz) of CP-751,871 after intravenous dosing in Cycle 1 (OM 36) was the correct outcome measure to be registered.
Secondary
Apparent Volume of Distribution (Vz/F) of CP-751,871 in 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.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to registration error: apparent volume of distribution (Vz/F) is for oral dose. Volume of Distribution (Vz) of CP-751,871 after intravenous dosing in Cycle 4 (OM 38) was the correct outcome measure to be registered.
Secondary
Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 38.4 mg*hr/L | Standard Deviation 7.1 |
| CP-751,871 0.4 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 1045 mg*hr/L | Standard Deviation 236 |
| CP-751,871 0.8 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 2040 mg*hr/L | Standard Deviation 621 |
| CP-751,871 1.5 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 5026 mg*hr/L | Standard Deviation 2516 |
| CP-751,871 3 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 10570 mg*hr/L | Standard Deviation 3369 |
| CP-751,871 6 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 26215 mg*hr/L | Standard Deviation 2520 |
| CP-751,871 10 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 38160 mg*hr/L | Standard Deviation 7757 |
| CP-751,871 20 mg/kg + Docetaxel | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 | 84916 mg*hr/L | Standard Deviation 25982 |
Secondary
Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 4
Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported since the actual dosing interval (tau) was longer than 3 weeks in some patients and AUC(0-d22) may not accurately represent multiple-dose exposure for these patients. Therefore only AUCtau, which represents exposure for the actual Cycle 4 interval, was reported for Cycle 4 (OM 40).
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle.
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: This OM was not reported because it is the same as Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) in Cycle 1 (OM 23), for both represented the planned 21-day dosing interval.
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4
Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 36.1 mg*hr/L | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 745 mg*hr/L | Standard Deviation 34.8 |
| CP-751,871 0.8 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 2978 mg*hr/L | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 11802 mg*hr/L | — |
| CP-751,871 3 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 26329 mg*hr/L | — |
| CP-751,871 6 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 55466 mg*hr/L | — |
| CP-751,871 10 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 65711 mg*hr/L | — |
| CP-751,871 20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 | 233578 mg*hr/L | Standard Deviation 105208 |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.4 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 949 mg*hr/L | — |
| CP-751,871 0.8 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 2744 mg*hr/L | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 6532 mg*hr/L | — |
| CP-751,871 3 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 7799 mg*hr/L | — |
| CP-751,871 10 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 47711 mg*hr/L | Standard Deviation 9305 |
| CP-751,871 20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 | 136026 mg*hr/L | — |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 4
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to registration error. AUCinf is not scientifically appropriate for repeated dosing (Cycle 4).
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 22.3 mg*hr/L | Standard Deviation 4.45 |
| CP-751,871 0.4 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 673 mg*hr/L | Standard Deviation 127 |
| CP-751,871 0.8 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 1685 mg*hr/L | Standard Deviation 879 |
| CP-751,871 1.5 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 4568 mg*hr/L | Standard Deviation 2953 |
| CP-751,871 3 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 10712 mg*hr/L | Standard Deviation 3147 |
| CP-751,871 6 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 26215 mg*hr/L | Standard Deviation 2520 |
| CP-751,871 10 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 39724 mg*hr/L | Standard Deviation 8380 |
| CP-751,871 20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 | 78106 mg*hr/L | Standard Deviation 37097 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 20.6 mg*hr/L | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 521 mg*hr/L | Standard Deviation 37.1 |
| CP-751,871 0.8 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 1728 mg*hr/L | Standard Deviation 596 |
| CP-751,871 1.5 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 11802 mg*hr/L | — |
| CP-751,871 3 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 26329 mg*hr/L | — |
| CP-751,871 6 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 55466 mg*hr/L | — |
| CP-751,871 10 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 45521 mg*hr/L | Standard Deviation 18562 |
| CP-751,871 20 mg/kg + Docetaxel | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 | 197090 mg*hr/L | Standard Deviation 122305 |
Secondary
Circulating Tumor Cells (CTCs), CTCs Expressing Insulin-like Growth Factor 1 Receptor (IGF-1R), and Circulating Endothelial Cells (CECs)
Time frame: Predose on Day 1 and on Day 8 of each cycle, and End of Study (28 days after the last CP-751,871 infusion)
Population: The data of CTCs and CTCs expressing IGF-IR were limited. Analyses of these biomarkers in the aggregate population were not feasible due to insufficient numbers. The data of CECs were not analyzed due to insufficient levels for quantification.
Secondary
Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 1.34 mg/L | Standard Deviation 0.365 |
| CP-751,871 0.4 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 7.81 mg/L | Standard Deviation 0.475 |
| CP-751,871 0.8 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 17.9 mg/L | Standard Deviation 6.79 |
| CP-751,871 1.5 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 33.4 mg/L | Standard Deviation 5.97 |
| CP-751,871 3 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 57.7 mg/L | Standard Deviation 23.7 |
| CP-751,871 6 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 129 mg/L | Standard Deviation 23.6 |
| CP-751,871 10 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 205 mg/L | Standard Deviation 39.5 |
| CP-751,871 20 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 | 382 mg/L | Standard Deviation 156 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 1.29 mg/L | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 6.91 mg/L | Standard Deviation 1.75 |
| CP-751,871 0.8 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 17.8 mg/L | Standard Deviation 2.13 |
| CP-751,871 1.5 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 54.7 mg/L | — |
| CP-751,871 3 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 103 mg/L | — |
| CP-751,871 6 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 188 mg/L | — |
| CP-751,871 10 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 311 mg/L | Standard Deviation 65.5 |
| CP-751,871 20 mg/kg + Docetaxel | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 | 658 mg/L | Standard Deviation 185 |
Secondary
Number of Participants With Objective Response (OR)
Number of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to 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: Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days)
Population: This outcome measure was not reported because data was available in individual participant listing only and not statistically summarized for the analysis.
Secondary
Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871
The development of HAHA is considered clinically relevant when temporally associated to the onset of adverse events or a significant decrease in the plasma concentrations of CP-751,871. The positive value is defined as ≥3.32.
Time frame: 30 minutes predose at each cycle, End of Study (28 days after the last CP-751,871 infusion), and 150 days after the last CP-751,871 infusion
Population: All enrolled participants who started treatment and had evaluable HAHA data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
| CP-751,871 0.4 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
| CP-751,871 0.8 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
| CP-751,871 1.5 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
| CP-751,871 3 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
| CP-751,871 6 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
| CP-751,871 10 mg/kg + Docetaxel | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 | 0 Participants |
Secondary
Observed Accumulation Ratio (Rac) of CP-751,871
AUCtao of Cycle 4 divided by AUC(0-d22) of Cycle 1
Time frame: 30 minutes prior to CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of CP-751,871 infusion; and 30 minutes prior to the next cycle CP-751,871 infusion (Day 22) in Cycle 1 and Cycle 4
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 0.852 Ratio | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 0.714 Ratio | Standard Deviation 0.236 |
| CP-751,871 0.8 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 1.48 Ratio | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 1.50 Ratio | — |
| CP-751,871 3 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 2.16 Ratio | — |
| CP-751,871 6 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 2.04 Ratio | — |
| CP-751,871 10 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 1.95 Ratio | — |
| CP-751,871 20 mg/kg + Docetaxel | Observed Accumulation Ratio (Rac) of CP-751,871 | 2.00 Ratio | Standard Deviation 0.35 |
Secondary
Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4
Cday22 is the measured CP-751,871 plasma concentration in blood sample collected at Day 22.
Time frame: Cycle 1: 30 minutes prior to the Cycle 2 CP-751,871 infusion (this is Day 22 for Cycle 1); Cycle 4: 30 minutes prior to the Cycle 5 CP-751,871 infusion (this is Day 22 for Cycle 4)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 0 mg/L | Standard Deviation 0 |
| CP-751,871 0.1-20 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 0 mg/L | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 0 mg/L | Standard Deviation 0 |
| CP-751,871 0.4 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 0 mg/L | Standard Deviation 0 |
| CP-751,871 0.8 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 0.185 mg/L | Standard Deviation 0.32 |
| CP-751,871 0.8 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 0.144 mg/L | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 2.11 mg/L | Standard Deviation 2.71 |
| CP-751,871 1.5 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 12.5 mg/L | — |
| CP-751,871 3 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 9.07 mg/L | Standard Deviation 7.17 |
| CP-751,871 3 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 32.2 mg/L | — |
| CP-751,871 6 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 30.4 mg/L | Standard Deviation 4.95 |
| CP-751,871 6 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 47.2 mg/L | — |
| CP-751,871 10 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 79.3 mg/L | — |
| CP-751,871 10 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 37.7 mg/L | Standard Deviation 15.4 |
| CP-751,871 20 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 1 | 84.5 mg/L | Standard Deviation 12.3 |
| CP-751,871 20 mg/kg + Docetaxel | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 | Day 22 of Cycle 4 | 199 mg/L | Standard Deviation 72.9 |
Secondary
Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.4 mg/kg + Docetaxel | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 68.5 hr | — |
| CP-751,871 0.8 mg/kg + Docetaxel | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 97.4 hr | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 151 hr | — |
| CP-751,871 3 mg/kg + Docetaxel | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 150 hr | — |
| CP-751,871 10 mg/kg + Docetaxel | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 224 hr | Standard Deviation 67 |
| CP-751,871 20 mg/kg + Docetaxel | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 | 174 hr | — |
Secondary
Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 4
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to insufficient data: the parameter was estimable in only 3 of 25 subjects.
Secondary
Systemic Clearance (CL) of CP-751,871 in Cycle 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.4 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 10.1 mL/day/kg | — |
| CP-751,871 0.8 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 7.00 mL/day/kg | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 6.67 mL/day/kg | — |
| CP-751,871 3 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 9.23 mL/day/kg | — |
| CP-751,871 10 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 5.17 mL/day/kg | Standard Deviation 0.99 |
| CP-751,871 20 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 1 | 3.53 mL/day/kg | — |
Secondary
Systemic Clearance (CL) of CP-751,871 in Cycle 4
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 70.6 mL/day/kg | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 12.90 mL/day/kg | Standard Deviation 0.59 |
| CP-751,871 0.8 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 6.84 mL/day/kg | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 3.05 mL/day/kg | — |
| CP-751,871 3 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 2.74 mL/day/kg | — |
| CP-751,871 6 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 2.68 mL/day/kg | — |
| CP-751,871 10 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 4.01 mL/day/kg | — |
| CP-751,871 20 mg/kg + Docetaxel | Systemic Clearance (CL) of CP-751,871 in Cycle 4 | 2.70 mL/day/kg | Standard Deviation 1.97 |
Secondary
Time of Last Quantifiable Time Point (Tlast) of CP-751,871 in Cycle 1 and Cycle 4
Blood samples were collected at timepoints prespecified in the study protocol. Tlast of CP-751,871 was the last time point when blood sample collected was quantifiable for CP-751,871.
Time frame: Cycle 1 and 4: prior to CP-751,871 infusion, at 1 hour post CP-751,871 infusion, and at 1, 3, 7 days post end of docetaxel infusion
Population: This OM was not reported due to registration error. This parameter was not planned or analyzed for this study.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 1.54 hr | Standard Deviation 0.067 |
| CP-751,871 0.4 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 8.76 hr | Standard Deviation 12 |
| CP-751,871 0.8 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 1.70 hr | Standard Deviation 0.146 |
| CP-751,871 1.5 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 9.41 hr | Standard Deviation 12.7 |
| CP-751,871 3 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 1.98 hr | Standard Deviation 0.06 |
| CP-751,871 6 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 3.21 hr | Standard Deviation 0.336 |
| CP-751,871 10 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 11.1 hr | Standard Deviation 11.5 |
| CP-751,871 20 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 | 8.67 hr | Standard Deviation 7.51 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 1.53 hr | — |
| CP-751,871 0.4 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 1.65 hr | Standard Deviation 0.109 |
| CP-751,871 0.8 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 1.59 hr | Standard Deviation 0.119 |
| CP-751,871 1.5 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 2.25 hr | — |
| CP-751,871 3 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 11.1 hr | — |
| CP-751,871 6 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 3.23 hr | — |
| CP-751,871 10 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 9.68 hr | Standard Deviation 10.71 |
| CP-751,871 20 mg/kg + Docetaxel | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 | 5.97 hr | Standard Deviation 0.296 |
Secondary
Time to Tumor Progression (TTP)
Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\])
Time frame: Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days)
Population: This outcome measure (OM) was not analyzed due to incomplete progression reporting, which could not permit accurate estimate of time to tumor progression (TTP).
Secondary
Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1
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 blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.4 mg/kg + Docetaxel | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 43.3 mL/kg | — |
| CP-751,871 0.8 mg/kg + Docetaxel | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 40.1 mL/kg | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 52.9 mL/kg | — |
| CP-751,871 3 mg/kg + Docetaxel | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 83.2 mL/kg | — |
| CP-751,871 10 mg/kg + Docetaxel | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 67.5 mL/kg | Standard Deviation 15.2 |
| CP-751,871 20 mg/kg + Docetaxel | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 | 37.5 mL/kg | — |
Secondary
Volume of Distribution at Steady State (Vss) of CP-751,871 in 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 blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to insufficient data: the parameter was estimable in only 3 of 25 subjects.
Secondary
Volume of Distribution (Vz) of CP-751,871 in Cycle 1
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.
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: All participants who started treatment and had evaluable PK data, excluding those who were enrolled in the PK drug interaction expansion cohort
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP-751,871 0.4 mg/kg + Docetaxel | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 41.7 mL/kg | — |
| CP-751,871 0.8 mg/kg + Docetaxel | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 40.9 mL/kg | — |
| CP-751,871 1.5 mg/kg + Docetaxel | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 55.1 mL/kg | — |
| CP-751,871 3 mg/kg + Docetaxel | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 83.1 mL/kg | — |
| CP-751,871 10 mg/kg + Docetaxel | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 67.9 mL/kg | Standard Deviation 15.5 |
| CP-751,871 20 mg/kg + Docetaxel | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 | 36.8 mL/kg | — |
Secondary
Volume of Distribution (Vz) of CP-751,871 in 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.
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to insufficient data: the parameter was estimable in only 3 of 25 subjects.
Other Pre-specified
Dose Normalized Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)(dn)) of CP-751,871 in Cycle 1
Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) divided by total dose
Time frame: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to registration error. This parameter was not planned or analyzed for this study.
Other Pre-specified
Dose Normalized Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)(dn)) of CP-751,871 in Cycle 4
Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) divided by total dose
Time frame: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
Population: This OM was not reported due to registration error. This parameter was not planned or analyzed for this study.