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Trial record 4 of 27 for:    PF-05280014

A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

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ClinicalTrials.gov Identifier: NCT02187744
Recruitment Status : Completed
First Posted : July 11, 2014
Results First Posted : April 7, 2017
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Early Breast Cancer
Interventions Biological: PF-05280014
Drug: Taxotere®
Drug: Paraplatin®
Biological: Trastuzumab-EU
Enrollment 226
Recruitment Details  
Pre-assignment Details A single participant was randomized but not treated; this participant was included in the ITT population, but not in the Participant Flow, Per Protocol, or Safety populations.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle. Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Period Title: Study
Started 113 [1] 112 [1]
Completed 109 106
Not Completed 4 6
Reason Not Completed
Participant refused further follow-up             1             0
Not specified             2             1
Lost to Follow-up             0             2
Related adverse event, not serious             0             2
Death             1             0
Related adverse event, serious non-fatal             0             1
[1]
Received treatment
Period Title: Treatment
Started 113 112
Completed 109 107
Not Completed 4 5
Reason Not Completed
Death             1             0
Related adverse event, serious non-fatal             0             1
Related adverse event, not serious             0             2
Lost to Follow-up             0             1
Not specified             2             0
Participant refused continued treatment             1             1
Arm/Group Title PF-05280014 Trastuzumab-EU Total
Hide Arm/Group Description Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle. Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle. Total of all reporting groups
Overall Number of Baseline Participants 114 112 226
Hide Baseline Analysis Population Description
All participants who were randomized into the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 114 participants 112 participants 226 participants
54.0  (11.9) 51.2  (12.7) 52.6  (12.3)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Female Number Analyzed 114 participants 112 participants 226 participants
114 112 226
1.Primary Outcome
Title Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.
Hide Description The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) >20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.
Time Frame Cycle 5
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Overall Number of Participants Analyzed 101 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
92.1
(85.0 to 96.5)
93.3
(85.9 to 97.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis to be tested in this study is the percentage of participants with steady state (Cycle 5) Ctrough >20 μg/mL of PF-05280014 is non-inferior to trastuzumab-EU using a margin of -12.5%.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.76
Confidence Interval (2-Sided) 95%
-8.02 to 6.49
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.70
Estimation Comments Stratified analysis was based on the normal approximation to the binomial distribution, adjusting for the randomization strata of primary tumor size, estrogen receptor status and by progesterone receptor status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The hypothesis to be tested in this study is the percentage of participants with steady state (Cycle 5) Ctrough >20 μg/mL of PF-05280014 is non-inferior to trastuzumab-EU using a margin of -12.5%.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.18
Confidence Interval (2-Sided) 95%
-8.59 to 6.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.78
Estimation Comments Unstratified analysis.
2.Secondary Outcome
Title Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.
Hide Description Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.
Time Frame Cycles 1 through 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Overall Number of Participants Analyzed 101 89
Mean (Standard Deviation)
Unit of Measure: μg/mL
Cycle 1/Day 1 0 hours N= 101, 88 2.313  (17.949) 1.318  (12.366)
Cycle 1/Day 1 1 hour N= 97, 80 160.4  (57.329) 164.8  (47.033)
Cycle 2/Day 21 0 hours N= 99, 88 24.29  (13.796) 27.20  (10.650)
Cycle 4/Day 63 0 hours N= 98, 89 33.43  (14.488) 37.33  (15.629)
Cycle 5/Day 84 0 hours N= 101, 87 35.01  (15.571) 40.44  (26.765)
Cycle 5/Day 84 1 hour N= 90, 80 137.0  (37.748) 138.8  (37.417)
Cycle 6/Day 105 0 hours N= 101, 89 37.77  (17.523) 40.10  (16.670)
3.Secondary Outcome
Title Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.
Hide Description Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.
Time Frame Cycle 6/End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Overall Number of Participants Analyzed 100 86
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
47.0
(36.9 to 57.2)
50.0
(39.0 to 61.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.81
Confidence Interval (2-Sided) 95%
-16.58 to 10.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.03
Estimation Comments Stratified analysis was based on the normal approximation to the binomial distribution, adjusting for the randomization strata of primary tumor size, estrogen receptor status and by progesterone receptor status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.00
Confidence Interval (2-Sided) 95%
-17.40 to 11.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.35
Estimation Comments Unstratified analysis.
4.Secondary Outcome
Title Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.
Hide Description ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.
Time Frame Cycle 6/End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Overall Number of Participants Analyzed 101 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
88.1
(80.2 to 93.7)
82.0
(72.5 to 89.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.96
Confidence Interval (2-Sided) 95%
-4.01 to 15.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.09
Estimation Comments Stratified analysis was based on the normal approximation to the binomial distribution, adjusting for the randomization strata of primary tumor size, estrogen receptor status and by progesterone receptor status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.10
Confidence Interval (2-Sided) 95%
-4.08 to 16.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.19
Estimation Comments Unstratified analysis.
5.Secondary Outcome
Title Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.
Hide Description The number of participants with positive (titer >=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.
Time Frame Cycles 1 through 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Overall Number of Participants Analyzed 113 112
Measure Type: Number
Unit of Measure: Number of participants
Cycle 1 (n=113,112) 0 1
Cycle 2 (n=111,112) 0 0
Cycle 4 (n=108,109) 0 0
Cycle 6 (n=108,108) 0 0
6.Secondary Outcome
Title Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.
Hide Description The number of participants with positive (NAb response >=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.
Time Frame Cycles 1 through 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
Overall Number of Participants Analyzed 113 112
Measure Type: Number
Unit of Measure: Number of participants
Cycle 1 (n=113,112) 0 0
Cycle 2 (n=110,112) 0 0
Cycle 4 (n=108,110) 0 0
Cycle 6 (n=108,108) 0 0
Time Frame Serious adverse events were captured from the beginning of the study drug treatment up to 6 months after the last dose. Treatment emergent adverse events were captured from the beginning of the study drug treatment up to 50 days after the last dose.
Adverse Event Reporting Description Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.
 
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle. Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.
All-Cause Mortality
PF-05280014 Trastuzumab-EU
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PF-05280014 Trastuzumab-EU
Affected / at Risk (%) Affected / at Risk (%)
Total   7/113 (6.19%)   6/112 (5.36%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  1/113 (0.88%)  2/112 (1.79%) 
Neutropenia  1  1/113 (0.88%)  1/112 (0.89%) 
Anaemia  1  0/113 (0.00%)  1/112 (0.89%) 
Pancytopenia  1  1/113 (0.88%)  0/112 (0.00%) 
Gastrointestinal disorders     
Proctitis  1  1/113 (0.88%)  0/112 (0.00%) 
Infections and infestations     
Device related sepsis  1  1/113 (0.88%)  0/112 (0.00%) 
Gastrointestinal infection  1  0/113 (0.00%)  1/112 (0.89%) 
Injection site abscess  1  1/113 (0.88%)  0/112 (0.00%) 
Tooth infection  1  0/113 (0.00%)  1/112 (0.89%) 
Injury, poisoning and procedural complications     
Hip fracture  1  0/113 (0.00%)  1/112 (0.89%) 
Investigations     
Blood creatinine increased  1  1/113 (0.88%)  0/112 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/113 (0.00%)  1/112 (0.89%) 
Hypokalaemia  1  0/113 (0.00%)  1/112 (0.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, version 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-05280014 Trastuzumab-EU
Affected / at Risk (%) Affected / at Risk (%)
Total   106/113 (93.81%)   106/112 (94.64%) 
Blood and lymphatic system disorders     
Anaemia  1  56/113 (49.56%)  51/112 (45.54%) 
Neutropenia  1  37/113 (32.74%)  41/112 (36.61%) 
Leukopenia  1  16/113 (14.16%)  25/112 (22.32%) 
Thrombocytopenia  1  16/113 (14.16%)  19/112 (16.96%) 
Febrile neutropenia  1  3/113 (2.65%)  6/112 (5.36%) 
Gastrointestinal disorders     
Nausea  1  38/113 (33.63%)  34/112 (30.36%) 
Diarrhoea  1  16/113 (14.16%)  19/112 (16.96%) 
Vomiting  1  7/113 (6.19%)  10/112 (8.93%) 
General disorders     
Asthenia  1  36/113 (31.86%)  23/112 (20.54%) 
Fatigue  1  15/113 (13.27%)  19/112 (16.96%) 
Pyrexia  1  6/113 (5.31%)  5/112 (4.46%) 
Investigations     
Alanine aminotransferase increased  1  7/113 (6.19%)  10/112 (8.93%) 
Aspartate aminotransferase increased  1  3/113 (2.65%)  7/112 (6.25%) 
Metabolism and nutrition disorders     
Decreased appetite  1  13/113 (11.50%)  9/112 (8.04%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  16/113 (14.16%)  8/112 (7.14%) 
Bone pain  1  13/113 (11.50%)  5/112 (4.46%) 
Nervous system disorders     
Peripheral sensory neuropathy  1  7/113 (6.19%)  4/112 (3.57%) 
Dysgeusia  1  4/113 (3.54%)  6/112 (5.36%) 
Neuropathy peripheral  1  6/113 (5.31%)  4/112 (3.57%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  72/113 (63.72%)  69/112 (61.61%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, version 19.0
It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Pfizer CT.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02187744     History of Changes
Other Study ID Numbers: B3271004
REFLECTIONS B327-04
2013-004679-11 ( EudraCT Number )
REFLECTIONS (B327-04) ( Other Identifier: Alias Study Number )
First Submitted: June 30, 2014
First Posted: July 11, 2014
Results First Submitted: February 22, 2017
Results First Posted: April 7, 2017
Last Update Posted: January 8, 2019