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Completed

NCT Number: NCT01653158

CP-751,871 In Combination With Docetaxel In Advance Non-hematologic Malignancies

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.

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Key information

Conditions

Advanced Non-Hematologic Malignancies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site

Sutton, Surrey, SM2 5PT, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CP-751,871

Drug

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).

docetaxel

Drug

Docetaxel up to 75 mg/m^2 was administered intravenously [IV] on Day 1 of each 3-week dosing cycle.

Primary outcomes

  1. Maximum Tolerated Dose (MTD)

    Time frame: Cycle 1 Day 1 through Cycle 1 Day 21

  2. Recommended Phase 2 Dose (RP2D)

    Time frame: Cycle 1 Day 1 through Cycle 1 Day 21

  3. Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) 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

    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)

  4. Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) 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

    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)

  5. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  6. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  7. Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) 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

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose

  8. Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) 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

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose

  9. 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

  10. 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

  11. Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) 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

    Maximum Observed Plasma Concentration (Cmax) divided by dose

  12. Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) 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

    Maximum Observed Plasma Concentration (Cmax) divided by dose

  13. 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

  14. 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

Secondary outcomes

  1. Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871

    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

    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.

  2. Number of Participants With Objective Response (OR)

    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)

    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.

  3. Time to Tumor Progression (TTP)

    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)

    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])

  4. 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)

  5. Systemic Clearance (CL) 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)

    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  6. Systemic Clearance (CL) 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)

    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  7. 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)

  8. 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)

  9. Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) 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)

    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.

  10. Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) 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)

    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.

  11. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) 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)

    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).

  12. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) 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)

    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).

  13. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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)

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  14. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 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)

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  15. Plasma Decay Half-Life (t1/2) 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)

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  16. Plasma Decay Half-Life (t1/2) 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)

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  17. 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)

  18. 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)

  19. Volume of Distribution at Steady State (Vss) 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)

    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.

  20. Volume of Distribution at Steady State (Vss) 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)

    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.

  21. Apparent Volume of Distribution (Vz/F) 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)

    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.

  22. Volume of Distribution (Vz) 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)

    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.

  23. Apparent Volume of Distribution (Vz/F) 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)

    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.

  24. Volume of Distribution (Vz) 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)

    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.

  25. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) 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)

    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.

  26. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) 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)

    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.

  27. Observed Accumulation Ratio (Rac) of CP-751,871

    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

    AUCtao of Cycle 4 divided by AUC(0-d22) of Cycle 1

  28. Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4

    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)

    Cday22 is the measured CP-751,871 plasma concentration in blood sample collected at Day 22.

  29. Time of Last Quantifiable Time Point (Tlast) of CP-751,871 in Cycle 1 and Cycle 4

    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

    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.

Other outcomes

  1. 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

    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)

    Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) divided by total dose

  2. 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

    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)

    Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) divided by total dose

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A Phase 1b Dose Escalation, Open-label Study Of CP-751,871 In Combination With Docetaxel In Advanced Non-hematologic Malignancies

Important dates

Study start
2005
Primary completion
2009
Study completion
2009
First posted
Jul 30, 2012
Registry last updated
Oct 30, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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