Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
MY TRIALS
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Register a trial
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01307267
Registration number
NCT01307267
Ethics application status
Date submitted
28/02/2011
Date registered
2/03/2011
Titles & IDs
Public title
A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
Query!
Scientific title
A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
Query!
Secondary ID [1]
0
0
2011-002799-17
Query!
Secondary ID [2]
0
0
B1641001
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin
0
0
Query!
Lymphoma, Follicular
0
0
Query!
Lymphoma, Large B-Cell, Diffuse
0
0
Query!
Carcinoma, Non-Small-Cell Lung
0
0
Query!
Carcinoma, Renal Cell
0
0
Query!
Carcinoma, Squamous Cell of Head and Neck
0
0
Query!
Malignant Melanoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Query!
Cancer
0
0
0
0
Query!
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Query!
Cancer
0
0
0
0
Query!
Non melanoma skin cancer
Query!
Cancer
0
0
0
0
Query!
Kidney
Query!
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Cancer
0
0
0
0
Query!
Lung - Non small cell
Query!
Cancer
0
0
0
0
Query!
Head and neck
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - PF-05082566
Treatment: Drugs - rituximab
Treatment: Drugs - PF-05082566
Experimental: Portion A - PF-05082566 single agent in patients with advanced cancer
Experimental: Portion B - PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
Treatment: Drugs: PF-05082566
Intravenous, Dose escalation, once per month
Treatment: Drugs: rituximab
Intravenous, 375 mg/m2, once per week for 4 weeks
Treatment: Drugs: PF-05082566
IV, Dose escalation, once per month
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
Query!
Assessment method [1]
0
0
DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade =3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade =3 hemolysis. Non-Hematologic: Grade =3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Query!
Timepoint [1]
0
0
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
Query!
Primary outcome [2]
0
0
Number of Participants With DLTs in First 2 Cycles of Portion B
Query!
Assessment method [2]
0
0
DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade =3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade =3 hemolysis. Non-Hematologic: Grade =3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Query!
Timepoint [2]
0
0
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
Query!
Secondary outcome [1]
0
0
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Query!
Assessment method [1]
0
0
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both non-serious AEs and SAEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Causality of AEs was determined by the investigator.
Query!
Timepoint [1]
0
0
Up to approximately 2 years
Query!
Secondary outcome [2]
0
0
Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Query!
Assessment method [2]
0
0
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Query!
Timepoint [2]
0
0
Up to approximately 2 years
Query!
Secondary outcome [3]
0
0
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Query!
Assessment method [3]
0
0
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells. The abnormalities with at least 1 participant are presented here.
Query!
Timepoint [3]
0
0
Up to approximately 2 years
Query!
Secondary outcome [4]
0
0
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Query!
Assessment method [4]
0
0
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. The abnormalities with at least 1 participant are presented here.
Query!
Timepoint [4]
0
0
Up to approximately 2 years
Query!
Secondary outcome [5]
0
0
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Query!
Assessment method [5]
0
0
For vital signs in Portion A, blood pressure and pulse rate were measured. Clinical significance was determined by the investigator.
Query!
Timepoint [5]
0
0
Up to approximately 2 years
Query!
Secondary outcome [6]
0
0
PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
Query!
Assessment method [6]
0
0
Cmax of PF-05082566 was observed directly from data.
Query!
Timepoint [6]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
Query!
Secondary outcome [7]
0
0
PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
Query!
Assessment method [7]
0
0
Ctrough of PF-05082566 was observed directly from data.
Query!
Timepoint [7]
0
0
Day 1 pre-dose of Cycle 2
Query!
Secondary outcome [8]
0
0
PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
Query!
Assessment method [8]
0
0
Tmax of PF-05082566 was observed directly from data as time of Cmax.
Query!
Timepoint [8]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Query!
Secondary outcome [9]
0
0
PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A
Query!
Assessment method [9]
0
0
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Query!
Timepoint [9]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Query!
Secondary outcome [10]
0
0
PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
Query!
Assessment method [10]
0
0
AUCinf = AUClast + (Clast\*/kel), where Clast\* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
Query!
Timepoint [10]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Query!
Secondary outcome [11]
0
0
PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
Query!
Assessment method [11]
0
0
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Query!
Timepoint [11]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Query!
Secondary outcome [12]
0
0
PF-05082566 Clearance (CL) in Portion A
Query!
Assessment method [12]
0
0
CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2. It was reported in units of milliliter per hour per kilogram (mL/hr/kg).
Query!
Timepoint [12]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Query!
Secondary outcome [13]
0
0
PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
Query!
Assessment method [13]
0
0
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Query!
Timepoint [13]
0
0
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Query!
Secondary outcome [14]
0
0
Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
Query!
Assessment method [14]
0
0
ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer\>=6.23.
Query!
Timepoint [14]
0
0
Up to approximately 2 years
Query!
Secondary outcome [15]
0
0
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
Query!
Assessment method [15]
0
0
Categorical summarization criteria for QTc interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate): 1) absolute value of \>450 to \<=480 milliseconds (msec), \>480 to \<=500 msec, \>500 msec; 2) a maximum change from baseline of \>30 to \<=60 msec or \>60 msec.
Query!
Timepoint [15]
0
0
Up to approximately 2 years
Query!
Secondary outcome [16]
0
0
Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
Query!
Assessment method [16]
0
0
Objective response: confirmed best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1. BOR of CR: target lesions and non-target diseases achieved CR, without new lesions. BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-progression of disease (non-PD), indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and \>=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
Query!
Timepoint [16]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [17]
0
0
Duration of Response in Portion A
Query!
Assessment method [17]
0
0
Duration of response: the time from first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1) to the date of first documentation of objective progression of disease (PD) or death due to any cause. Objective PD per RECIST version 1.1: \>=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 millimeters (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions. This outcome measure reports the individual values for evaluable participants (instead of medians etc) due to the limited number of events.
Query!
Timepoint [17]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [18]
0
0
Time to Response in Portion A
Query!
Assessment method [18]
0
0
Time to response: the time from Cycle 1 Day 1 to the first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1). BOR of CR: target lesions and non-target diseases achieved CR, without new lesions. BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes decreased to normal size); PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and \>=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
Query!
Timepoint [18]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [19]
0
0
Progression-Free Survival in Portion A
Query!
Assessment method [19]
0
0
Progression-free survival: the time from Cycle 1 Day 1 to the date of the first documentation of objective PD or death due to any cause, whichever occurred first. Objective PD per RECIST version 1.1: \>=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; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
Query!
Timepoint [19]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [20]
0
0
Overall Survival in Portion A
Query!
Assessment method [20]
0
0
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Query!
Timepoint [20]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [21]
0
0
Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
Query!
Assessment method [21]
0
0
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both non-serious AEs and SAEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Causality of AEs was determined by the investigator.
Query!
Timepoint [21]
0
0
Up to approximately 4 years
Query!
Secondary outcome [22]
0
0
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B
Query!
Assessment method [22]
0
0
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Query!
Timepoint [22]
0
0
Up to approximately 4 years
Query!
Secondary outcome [23]
0
0
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Query!
Assessment method [23]
0
0
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells. The abnormalities with at least 1 participant are presented here.
Query!
Timepoint [23]
0
0
Up to approximately 2 years
Query!
Secondary outcome [24]
0
0
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Query!
Assessment method [24]
0
0
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. The abnormalities with at least 1 participant are presented here.
Query!
Timepoint [24]
0
0
Up to approximately 2 years
Query!
Secondary outcome [25]
0
0
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
Query!
Assessment method [25]
0
0
For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured. Clinical significance was determined by the investigator.
Query!
Timepoint [25]
0
0
Up to approximately 2 years
Query!
Secondary outcome [26]
0
0
PF-05082566 Cmax in Portion B
Query!
Assessment method [26]
0
0
Cmax of PF-05082566 was observed directly from data.
Query!
Timepoint [26]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Query!
Secondary outcome [27]
0
0
PF-05082566 Ctrough in Portion B
Query!
Assessment method [27]
0
0
Ctrough of PF-05082566 was observed directly from data.
Query!
Timepoint [27]
0
0
Day 1 pre-dose of Cycle 2
Query!
Secondary outcome [28]
0
0
PF-05082566 Tmax in Portion B
Query!
Assessment method [28]
0
0
Tmax of PF-05082566 was observed directly from data as time of Cmax.
Query!
Timepoint [28]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Query!
Secondary outcome [29]
0
0
PF-05082566 AUClast in Portion B
Query!
Assessment method [29]
0
0
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Query!
Timepoint [29]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Query!
Secondary outcome [30]
0
0
PF-05082566 AUCinf in Portion B
Query!
Assessment method [30]
0
0
AUCinf = AUClast + (Clast\*/kel), where Clast\* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
Query!
Timepoint [30]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
Query!
Secondary outcome [31]
0
0
PF-05082566 AUCtau in Portion B
Query!
Assessment method [31]
0
0
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Query!
Timepoint [31]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Query!
Secondary outcome [32]
0
0
PF-05082566 CL in Portion B
Query!
Assessment method [32]
0
0
CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
Query!
Timepoint [32]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Query!
Secondary outcome [33]
0
0
PF-05082566 Vss in Portion B
Query!
Assessment method [33]
0
0
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Query!
Timepoint [33]
0
0
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Query!
Secondary outcome [34]
0
0
Rituximab Cmax and Ctrough in Portion B
Query!
Assessment method [34]
0
0
Cmax and Ctrough of rituximab were observed directly from data.
Query!
Timepoint [34]
0
0
Day 1 pre-dose of Cycle 2
Query!
Secondary outcome [35]
0
0
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
Query!
Assessment method [35]
0
0
ADA for PF-05082566 and rituximab was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer\>=6.23. Positive ADA for rituximab: titer\>=1.88.
Query!
Timepoint [35]
0
0
Up to approximately 2 years
Query!
Secondary outcome [36]
0
0
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B
Query!
Assessment method [36]
0
0
Categorical summarization criteria for QTc interval: 1) absolute value of \>450 to \<=480 milliseconds (msec), \>480 to \<=500 msec, \>500 msec; 2) a maximum change from baseline of \>30 to \<=60 msec or \>60 msec.
Query!
Timepoint [36]
0
0
Up to approximately 2 years
Query!
Secondary outcome [37]
0
0
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B
Query!
Assessment method [37]
0
0
Objective Response in Portion B was defined as BOR of CR or PR according to Cheson 2007 criteria. BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or \>=50% decrease in the sum of the product diameters \[SPD\] of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion \>=15 mm in greatest transverse diameter \[GTD\], unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
Query!
Timepoint [37]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [38]
0
0
Duration of Response in Portion B
Query!
Assessment method [38]
0
0
Duration of Response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from first documentation of objective response to the date of first documentation of objective PD or death due to any cause. Objective PD per Cheson 2007 was defined as: PD of index lesions (\>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion \>=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
Query!
Timepoint [38]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [39]
0
0
Time to Response in Portion B
Query!
Assessment method [39]
0
0
Time to response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from Cycle 1 Day 1 to the first documentation of objective response. BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or \>=50% decrease in the SPD of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion \>=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
Query!
Timepoint [39]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [40]
0
0
Progression-Free Survival in Portion B
Query!
Assessment method [40]
0
0
Progression-free survival in Portion B was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective PD (per Cheson 2007) or death due to any cause, whichever occurred first. Objective PD per Cheson 2007 was defined as: PD of index lesions (\>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion \>=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
Query!
Timepoint [40]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Secondary outcome [41]
0
0
Overall Survival in Portion B
Query!
Assessment method [41]
0
0
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Query!
Timepoint [41]
0
0
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Query!
Eligibility
Key inclusion criteria
Inclusion Criteria
* Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
* Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
* Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
* ECOG performance status of = 1.
* Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) = 1.5 x 109/L, platelet count =100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC = 1.0 x 109/L, platelet count = 75 x 109/L, and hemoglobin = 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
* Serum creatinine = 2 x ULN or estimated creatinine clearance = 50 ml/min.
* Total serum bilirubin = 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT = 2.5 x ULN.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Exclusion Criteria
* Patients with known symptomatic brain metastases requiring steroids.
* Prior allogeneic hematopoietic stem cell transplant.
* Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
* Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
* Autoimmune disorders and other diseases that compromise or impair the immune system.
* Unstable or serious concurrent medical conditions in the previous 6 months.
* Prior therapy with any anti CD137 monoclonal antibody.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
21/06/2011
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
20/02/2019
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
190
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Peter MacCallum Cancer Centre - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
3000 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
District of Columbia
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Georgia
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Massachusetts
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Michigan
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Missouri
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
New York
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Texas
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Washington
Query!
Country [10]
0
0
France
Query!
State/province [10]
0
0
RENNES cedex 9
Query!
Country [11]
0
0
Italy
Query!
State/province [11]
0
0
BO
Query!
Country [12]
0
0
Italy
Query!
State/province [12]
0
0
MI
Query!
Country [13]
0
0
Japan
Query!
State/province [13]
0
0
Chiba
Query!
Country [14]
0
0
Japan
Query!
State/province [14]
0
0
Akita
Query!
Country [15]
0
0
Japan
Query!
State/province [15]
0
0
Tokyo
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Pfizer
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
Query!
Trial website
https://clinicaltrials.gov/study/NCT01307267
Query!
Trial related presentations / publications
Gopal AK, Levy R, Houot R, Patel SP, Popplewell L, Jacobson C, Mu XJ, Deng S, Ching KA, Chen Y, Davis CB, Huang B, Fly KD, Thall A, Woolfson A, Bartlett NL. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6. Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816-1823. doi: 10.1158/1078-0432.CCR-17-1922. Epub 2018 Mar 16.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Pfizer CT.gov Call Center
Query!
Address
0
0
Pfizer
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
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.
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/67/NCT01307267/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/67/NCT01307267/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT01307267