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A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer

Primary Purpose

Metastatic Colorectal Cancer

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-05212384
irinotecan
Cetuximab
Irinotecan
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring metastatic colorectal cancer, colorectal cancer, KRAS, colon cancer, mCRC, CRC, PF-05212384, KRAS wild type colorectal cancer, irinotecan, cetuximab, NRAS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • KRAS and NRAS wild type metastatic colorectal cancer
  • Progression following treatment for colorectal cancer with irinotecan, oxaliplatin and fluoropyrimidine therapy in the metastatic setting.
  • Eastern Cooperative Oncology Group [ECOG] Performance Status of 0, 1, or 2
  • At least one measurable lesion by Response Evaluation Criterion in Solid Tumors [RECIST]

Exclusion Criteria:

  • More than 2 prior cytotoxic chemotherapy regimens for metastatic colorectal cancer.
  • Prior treatment with a PI3K, mTOR, AKT or EGFR inhibitor
  • Patients who have discontinued treatment with prior irinotecan therapy due to toxicity.
  • Prior radiation to the pelvis or abdomen
  • Patients with history of interstitial lung disease.

Sites / Locations

  • CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
  • Drug Management Only: UCLA West Medical Pharmacy, Att: Steven L Wong, Pharm D
  • Drug Management Only: UCLA West Medical Pharmacy
  • UCLA West Medical Pharmacy
  • Regulatory Management Only: TRIO-US Central Administration
  • TRIO-US Central Administration (Regulatory Management only)
  • TRIO_US
  • West Valley Hematology/Oncology Med Group
  • Siteman Cancer Center - West County
  • Barnes-Jewish Hospital
  • Washington University School of Medicine
  • Siteman Cancer Center - South County
  • Siteman Cancer Center - St Peters
  • Regulatory Office: Comprehensive Cancer Centers of Nevada
  • Comprehensive Cancer Centers of Nevada
  • Comprehensive Cancer Centers of Nevada
  • Comprehensive Cancer Centers of Nevada
  • Comprehensive Cancer Centers of Nevada
  • Comprehensive Cancer Centers of Nevada
  • Roswell Park Cancer Institute
  • Kadlec Clinic Hematology and Oncology
  • Kadlec Medical Center
  • Outpatient Imaging Center
  • Spokane Valley Cancer Center
  • Medical Oncology Associates, PS
  • Aichi cancer center central hospital
  • National Cancer Center Hospital East
  • National Cancer Center
  • Seoul National University Hospital / Department of Internal Medicine
  • Samsung Medical Center
  • Asan Medical Center
  • Hospital General Universitario Gregorio Marañón

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

PF-05212384 plus Irinotecan

Cetuximab plus Irinotecan

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) as Assessed by Investigators
Progression-free survival (PFS) was the time from the first dose of study treatment to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. Median PFS was estimated based on the Kaplan-Meier method.

Secondary Outcome Measures

Number of Participants With Unacceptable Toxicity in Cycle 1 (Japanese LIC Only)
Unacceptable toxicity (according to Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0) was any of the following occurrences: (1) Grade 4 neutropenia >7 days, or febrile neutropenia, or Grade 4 thrombocytopenia; (2) Grade >=3 nausea/vomiting despite optimal antiemetic treatment, or Grade >=3 diarrhea despite optimal anti diarrheal treatment; (3) unmanageable Grade >=3 hyperglycemia; (4) mean QTc interval (time from electrocardiogram [ECG] Q wave to the end of the T wave corresponding to electrical systole, corrected for heart rate) >501 msec in triplicate 12-lead ECG, or myocardial infarction, or ventricular arrhythmia; (5) Grade >=3 non-hematologic toxicity; (6) treatment delay of >=2 weeks due to study drug related toxicity; (7) persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses of both PF-05212384 and irinotecan during Cycle 1; (8) Grade >=2 respiratory toxicities.
Percentage of Participants With Objective Response
Percentage of participants with objective response was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1. Confirmed PR was defined as disappearance of all target lesions. Confirmed PR was defined as >=30% decrease in sum of the longest dimensions of the target lesions taking the baseline sum as a reference. Confirmed responses were those that persisted on repeat imaging study >=4 weeks after initial documentation of response.
Duration of Response
For participants with an objective response (CR or PR), duration of response was defined as the time from first documentation of CR or PR to date of first documentation of objective progression or death. Date of first documentation of progression and date of first documentation of CR or PR were based on Investigator's assessment of response.
Overall Survival (OS)
Overall survival (OS) was defined as the duration from enrollment to death. Participants last known to be alive were censored at date of last contact.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE was defined as any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.0 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
Number of Participants With Laboratory Test (Hematology) Abnormalities
The following hematology parameters were evaluated in this study: hemoglobin, white blood cells (WBC) with differential, and platelets.
Number of Participants With Laboratory Test (Chemistry) Abnormalities
The following chemistry parameters were evaluated in this study: sodium, potassium, magnesium, chloride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, blood urea nitrogen (BUN) or urea, creatinine, total calcium, glycosylated hemoglobin (HbA1c), glucose, uric acid, phosphorus or phosphate, insulin, and C-peptide.
Number of Participants With Laboratory Test (Urinalysis) Abnormalities
Urinalysis included urine dipstick for protein and blood: if positive, perform a microscopic analysis. Number of participants with urine protein tested positive is presented.
Number of Participants With Laboratory Test (Coagulation) Abnormalities
Coagulation analysis included partial thromboplastin time (PTT) and international normalized ratio (INR) or prothrombin time (PT).
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
The number of participants with ECG post-baseline maximum absolute values meeting the following criteria was reported: (1) maximum QTc interval ranged from 450 to 480 msec; >480-500 msec; >500 msec; (2) maximum QTcB (QT corrected for heart rate using Bazett's formula) interval ranged from 450 to 480 msec; >480-500 msec; >500 msec; (3) maximum QTcF (QT corrected for heart rate using Fridericia's formula) interval ranged from 450 to 480 msec; >480-500 msec; >500 msec.
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
The number of participants with ECG maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum QTc interval increase from baseline >30 msec and ≤60 msec; criterion B: maximum QTc interval increase from baseline >60 msec; criterion C: maximum QTcB interval increase from baseline >30 msec and ≤60 msec; criterion D: maximum QTcB interval increase from baseline >60 msec; criterion E: maximum QTcF interval increase from baseline >30 msec and ≤60 msec; criterion F: maximum QTcF interval increase from baseline >60 msec.
Maximum Plasma Concentration (Cmax) of PF-05212384
Cmax of PF-05212384 was observed directly from data.
Maximum Plasma Concentration (Cmax) of Irinotecan
Cmax of irinotecan was observed directly from data.
Maximum Plasma Concentration (Cmax) of SN-38
SN-38 is an irinotecan metabolite. Cmax of SN-38 was observed directly from data.
Time for Maximum Plasma Concentration (Tmax) of PF-05212384
Tmax of PF-05212384 was observed directly from data as time of first occurrence.
Time for Maximum Plasma Concentration (Tmax) of Irinotecan
Tmax of irinotecan was observed directly from data as time of first occurrence.
Time for Maximum Plasma Concentration (Tmax) of SN-38
SN-38 is an irinotecan metabolite. Tmax of SN-38 was observed directly from data as time of first occurrence.
Terminal Elimination Half Life (t½) of PF-05212384
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Terminal Elimination Half Life (t½) of Irinotecan
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Terminal Elimination Half Life (t½) of SN-38
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of PF-05212384
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of PF-05212384 was determined using linear/log trapezoidal method.
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of Irinotecan
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of irinotecan was determined using linear/log trapezoidal method.
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of SN-38
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of SN-38 (an irinotecan metabolite) was determined using linear/log trapezoidal method.
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05212384
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of PF-05212384 was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Irinotecan
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of irinotecan was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of SN-38
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of SN-38 (an irinotecan metabolite) was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Levels of Signaling Proteins in Paired and Single Tumor Biopsies
Pre defined signaling proteins included Akt (protein kinase B), p-Akt (phosphorylated Akt), p-S6 (phosphorylated ribosomal protein S6), p-Met (phosphorylated Met, a receptor tyrosine kinase), p-mTOR (phosphorylated mammalian target of rapamycin), EGFR (epithelial growth factor receptor), and p-EGFR (phosphorylated EGFR).
Number of Participants With Expression of Pre-defined Gene Sequences in Biopsied Tumor Tissues
Pre-defined gene sequences were those related to EGFR, PI3K (phosphoinositide-3 kinase) and other oncogenic pathways; examples included but were not limited to PIK3CA (this gene encodes the catalytic subunit of PI3K), PIK3R1 (this gene encodes the regulatory subunit of PI3K), KRAS, NRAS and BRAF (this gene encodes serine/threonine-protein kinase B-Raf) sequences and PIK3CA gene amplification. Due to early termination of this study, these pre-defined gene sequences were not analyzed, except for KRAS and NRAS. Number of participants who had KRAS and NRAS wild type status confirmed by the central laboratory is presented.
Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C)
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was used in this study to assess Health-Related Quality of Life (HRQoL) and CRC-related symptoms in participants enrolled to the randomized portion of the study. The FACT-C is part of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system, a comprehensive and extensive set of self-reported instruments for the assessment of health-related quality of life in participants with cancer or other chronic illnesses.

Full Information

First Posted
August 15, 2013
Last Updated
December 19, 2018
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01925274
Brief Title
A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer
Official Title
A RANDOMIZED PHASE 2 STUDY OF PF-05212384 PLUS IRINOTECAN VERSUS CETUXIMAB PLUS IRINOTECAN IN PATIENTS WITH KRAS AND NRAS WILD TYPE METASTATIC COLORECTAL CANCER
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
Enrollment to the study was terminated on 11Nvo2014 due to slow recruitment. There were no safety or efficacy issues that contributed to this decision.
Study Start Date
November 15, 2013 (Actual)
Primary Completion Date
April 6, 2016 (Actual)
Study Completion Date
April 6, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will investigate whether the combination of PF-05212384 plus Irinotecan improves progression free survival in patients with KRAS and NRAS wild type metastatic colorectal cancer when compared with the combination of cetuximab plus Irinotecan. A Japanese Lead in Cohort will assess the safety of the combination of PF-05212384 + irinotecan in patients enrolled at Japanese sites.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
metastatic colorectal cancer, colorectal cancer, KRAS, colon cancer, mCRC, CRC, PF-05212384, KRAS wild type colorectal cancer, irinotecan, cetuximab, NRAS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
PF-05212384 plus Irinotecan
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Cetuximab plus Irinotecan
Intervention Type
Drug
Intervention Name(s)
PF-05212384
Other Intervention Name(s)
PKI-587
Intervention Description
30 minute IV infusion of PF-05212384 on days 2, 9, 16 and 23 of each cycle. Intra-patient dose escalation will commence with 110mg and will increase depending on tolerability.
Intervention Type
Drug
Intervention Name(s)
irinotecan
Other Intervention Name(s)
Camptosar, Campto, CPT-11
Intervention Description
90 minutes IV infusion of irinotecan 180mg/m^2 on days 1 and 15 of each cycle
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
120 minute IV infusion of cetuximab 400mg/m^2 on cycle 1 day 1; 60 minute IV infusion of cetuximab on days 8, 15, and 22 of each cycle, and on day 1 of each cycle after cycle 1
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar, Campto, CPT-11
Intervention Description
90 minutes IV infusion of Irinotecan 180mg/m^2 on days 1 and 15 of each cycle
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) as Assessed by Investigators
Description
Progression-free survival (PFS) was the time from the first dose of study treatment to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. Median PFS was estimated based on the Kaplan-Meier method.
Time Frame
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary Outcome Measure Information:
Title
Number of Participants With Unacceptable Toxicity in Cycle 1 (Japanese LIC Only)
Description
Unacceptable toxicity (according to Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0) was any of the following occurrences: (1) Grade 4 neutropenia >7 days, or febrile neutropenia, or Grade 4 thrombocytopenia; (2) Grade >=3 nausea/vomiting despite optimal antiemetic treatment, or Grade >=3 diarrhea despite optimal anti diarrheal treatment; (3) unmanageable Grade >=3 hyperglycemia; (4) mean QTc interval (time from electrocardiogram [ECG] Q wave to the end of the T wave corresponding to electrical systole, corrected for heart rate) >501 msec in triplicate 12-lead ECG, or myocardial infarction, or ventricular arrhythmia; (5) Grade >=3 non-hematologic toxicity; (6) treatment delay of >=2 weeks due to study drug related toxicity; (7) persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses of both PF-05212384 and irinotecan during Cycle 1; (8) Grade >=2 respiratory toxicities.
Time Frame
28 days
Title
Percentage of Participants With Objective Response
Description
Percentage of participants with objective response was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1. Confirmed PR was defined as disappearance of all target lesions. Confirmed PR was defined as >=30% decrease in sum of the longest dimensions of the target lesions taking the baseline sum as a reference. Confirmed responses were those that persisted on repeat imaging study >=4 weeks after initial documentation of response.
Time Frame
2 years
Title
Duration of Response
Description
For participants with an objective response (CR or PR), duration of response was defined as the time from first documentation of CR or PR to date of first documentation of objective progression or death. Date of first documentation of progression and date of first documentation of CR or PR were based on Investigator's assessment of response.
Time Frame
2 years
Title
Overall Survival (OS)
Description
Overall survival (OS) was defined as the duration from enrollment to death. Participants last known to be alive were censored at date of last contact.
Time Frame
2 years
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE was defined as any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Time Frame
Administration of the first dose of study drug through 28 calendar days after the last administration of study drug
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Description
TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.0 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
Time Frame
Administration of the first dose of study drug through 28 calendar days after the last administration of study drug
Title
Number of Participants With Laboratory Test (Hematology) Abnormalities
Description
The following hematology parameters were evaluated in this study: hemoglobin, white blood cells (WBC) with differential, and platelets.
Time Frame
2 years
Title
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Description
The following chemistry parameters were evaluated in this study: sodium, potassium, magnesium, chloride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, blood urea nitrogen (BUN) or urea, creatinine, total calcium, glycosylated hemoglobin (HbA1c), glucose, uric acid, phosphorus or phosphate, insulin, and C-peptide.
Time Frame
2 years
Title
Number of Participants With Laboratory Test (Urinalysis) Abnormalities
Description
Urinalysis included urine dipstick for protein and blood: if positive, perform a microscopic analysis. Number of participants with urine protein tested positive is presented.
Time Frame
2 years
Title
Number of Participants With Laboratory Test (Coagulation) Abnormalities
Description
Coagulation analysis included partial thromboplastin time (PTT) and international normalized ratio (INR) or prothrombin time (PT).
Time Frame
2 years
Title
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Description
The number of participants with ECG post-baseline maximum absolute values meeting the following criteria was reported: (1) maximum QTc interval ranged from 450 to 480 msec; >480-500 msec; >500 msec; (2) maximum QTcB (QT corrected for heart rate using Bazett's formula) interval ranged from 450 to 480 msec; >480-500 msec; >500 msec; (3) maximum QTcF (QT corrected for heart rate using Fridericia's formula) interval ranged from 450 to 480 msec; >480-500 msec; >500 msec.
Time Frame
2 years
Title
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Description
The number of participants with ECG maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum QTc interval increase from baseline >30 msec and ≤60 msec; criterion B: maximum QTc interval increase from baseline >60 msec; criterion C: maximum QTcB interval increase from baseline >30 msec and ≤60 msec; criterion D: maximum QTcB interval increase from baseline >60 msec; criterion E: maximum QTcF interval increase from baseline >30 msec and ≤60 msec; criterion F: maximum QTcF interval increase from baseline >60 msec.
Time Frame
2 years
Title
Maximum Plasma Concentration (Cmax) of PF-05212384
Description
Cmax of PF-05212384 was observed directly from data.
Time Frame
Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
Title
Maximum Plasma Concentration (Cmax) of Irinotecan
Description
Cmax of irinotecan was observed directly from data.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Maximum Plasma Concentration (Cmax) of SN-38
Description
SN-38 is an irinotecan metabolite. Cmax of SN-38 was observed directly from data.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Time for Maximum Plasma Concentration (Tmax) of PF-05212384
Description
Tmax of PF-05212384 was observed directly from data as time of first occurrence.
Time Frame
Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
Title
Time for Maximum Plasma Concentration (Tmax) of Irinotecan
Description
Tmax of irinotecan was observed directly from data as time of first occurrence.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Time for Maximum Plasma Concentration (Tmax) of SN-38
Description
SN-38 is an irinotecan metabolite. Tmax of SN-38 was observed directly from data as time of first occurrence.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Terminal Elimination Half Life (t½) of PF-05212384
Description
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time Frame
Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
Title
Terminal Elimination Half Life (t½) of Irinotecan
Description
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Terminal Elimination Half Life (t½) of SN-38
Description
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of PF-05212384
Description
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of PF-05212384 was determined using linear/log trapezoidal method.
Time Frame
Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.
Title
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of Irinotecan
Description
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of irinotecan was determined using linear/log trapezoidal method.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of SN-38
Description
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of SN-38 (an irinotecan metabolite) was determined using linear/log trapezoidal method.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05212384
Description
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of PF-05212384 was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time Frame
Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.
Title
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Irinotecan
Description
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of irinotecan was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of SN-38
Description
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of SN-38 (an irinotecan metabolite) was calculated using the formula: AUCinf = AUClast + (Clast*/kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time Frame
Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
Title
Levels of Signaling Proteins in Paired and Single Tumor Biopsies
Description
Pre defined signaling proteins included Akt (protein kinase B), p-Akt (phosphorylated Akt), p-S6 (phosphorylated ribosomal protein S6), p-Met (phosphorylated Met, a receptor tyrosine kinase), p-mTOR (phosphorylated mammalian target of rapamycin), EGFR (epithelial growth factor receptor), and p-EGFR (phosphorylated EGFR).
Time Frame
2 years
Title
Number of Participants With Expression of Pre-defined Gene Sequences in Biopsied Tumor Tissues
Description
Pre-defined gene sequences were those related to EGFR, PI3K (phosphoinositide-3 kinase) and other oncogenic pathways; examples included but were not limited to PIK3CA (this gene encodes the catalytic subunit of PI3K), PIK3R1 (this gene encodes the regulatory subunit of PI3K), KRAS, NRAS and BRAF (this gene encodes serine/threonine-protein kinase B-Raf) sequences and PIK3CA gene amplification. Due to early termination of this study, these pre-defined gene sequences were not analyzed, except for KRAS and NRAS. Number of participants who had KRAS and NRAS wild type status confirmed by the central laboratory is presented.
Time Frame
2 years
Title
Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C)
Description
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was used in this study to assess Health-Related Quality of Life (HRQoL) and CRC-related symptoms in participants enrolled to the randomized portion of the study. The FACT-C is part of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system, a comprehensive and extensive set of self-reported instruments for the assessment of health-related quality of life in participants with cancer or other chronic illnesses.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: KRAS and NRAS wild type metastatic colorectal cancer Progression following treatment for colorectal cancer with irinotecan, oxaliplatin and fluoropyrimidine therapy in the metastatic setting. Eastern Cooperative Oncology Group [ECOG] Performance Status of 0, 1, or 2 At least one measurable lesion by Response Evaluation Criterion in Solid Tumors [RECIST] Exclusion Criteria: More than 2 prior cytotoxic chemotherapy regimens for metastatic colorectal cancer. Prior treatment with a PI3K, mTOR, AKT or EGFR inhibitor Patients who have discontinued treatment with prior irinotecan therapy due to toxicity. Prior radiation to the pelvis or abdomen Patients with history of interstitial lung disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Drug Management Only: UCLA West Medical Pharmacy, Att: Steven L Wong, Pharm D
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7349
Country
United States
Facility Name
Drug Management Only: UCLA West Medical Pharmacy
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7349
Country
United States
Facility Name
UCLA West Medical Pharmacy
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7349
Country
United States
Facility Name
Regulatory Management Only: TRIO-US Central Administration
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
TRIO-US Central Administration (Regulatory Management only)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
TRIO_US
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
West Valley Hematology/Oncology Med Group
City
Northridge
State/Province
California
ZIP/Postal Code
91328
Country
United States
Facility Name
Siteman Cancer Center - West County
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center - South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
Siteman Cancer Center - St Peters
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Facility Name
Regulatory Office: Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89014
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89074
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Kadlec Clinic Hematology and Oncology
City
Kennewick
State/Province
Washington
ZIP/Postal Code
99336
Country
United States
Facility Name
Kadlec Medical Center
City
Richland
State/Province
Washington
ZIP/Postal Code
99352
Country
United States
Facility Name
Outpatient Imaging Center
City
Richland
State/Province
Washington
ZIP/Postal Code
99352
Country
United States
Facility Name
Spokane Valley Cancer Center
City
Spokane Valley
State/Province
Washington
ZIP/Postal Code
99216
Country
United States
Facility Name
Medical Oncology Associates, PS
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
Facility Name
Aichi cancer center central hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
National Cancer Center
City
Goyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
410-769
Country
Korea, Republic of
Facility Name
Seoul National University Hospital / Department of Internal Medicine
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Hospital General Universitario Gregorio Marañón
City
Madrid
ZIP/Postal Code
28009
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B2151005&StudyName=A%20Study%20Of%20PF-05212384%20Plus%20Irinotecan%20Vs%20Cetuximab%20Plus%20Irinotecan%20In%20Patients%20With%20KRAS%20And%20NRAS%20Wild%20Type%20Metastatic%20Colorectal%20Can
Description
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Learn more about this trial

A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer

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