Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies
Primary Purpose
Metastatic Cancer Pancreas
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PF-03084014
Gemcitabine
Nab-paclitaxel
PF-03084014
Gemcitabine
Nab-paclitaxel
Gemcitabine
Nab-paclitaxel
Sponsored by

About this trial
This is an interventional treatment trial for Metastatic Cancer Pancreas
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically diagnosis of metastatic ductal adenocarcinoma of the pancreas.
- No prior radiotherapy, surgery chemotherapy or investigational therapy for metastatic disease. Prior adjuvant therapy with 5-FU or gemcitabine (± gemcitabine post radiation) administered as radiosensitizer allowed, provided at least 6 months have elapsed between the last dose and study registration
- Tumor tissue available (Archival 6 months old or de novo biopsy)
- Measurable disease as per RECIST 1.1
- Performance Status (ECOG) 0 or 1
Exclusion Criteria:
- Symptomatic brain metastases requiring steroids
- Prior therapy with gamma secretase inhibitors or other Notch pathway inhibitor
- Major surgery within 4 weeks of registration in the current study
- Known hypersensitivity to gemcitabine or nab-paclitaxel or any of the excipients
- Current or anticipated need for food or drugs that are strong/moderate CYP3A4 inhibitors or inducers
- Diagnosis of any second malignancy within 3 years prior to registration
Sites / Locations
- Anschutz Inpatient Pavilion
- University of Colorado Cancer Center
- University of Colorado Denver, CTO (CTRC)
- University of Rochester Investigational Drug Pharmacy
- University of Rochester
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Phase 1
Phase 2 Arm A
Phase 2 Arm B
Arm Description
PF-03084014 in combination with gemcitabine and nab-paclitaxel
PF-03084014 in combination with gemcitabine and nab-paclitaxel
Gemcitabine plus nab-Paclitaxel
Outcomes
Primary Outcome Measures
Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
DLT was defined as any of the following events occurring during the first cycle of treatment and considered at least possibly-related to study medication: any Grade 3 or 4 clinically-relevant non-hematologic and/or hematologic toxicity, delay of more than 2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.
Overall Survival (OS) in Phase 2
Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Secondary Outcome Measures
Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.
Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.
Number of Participants With Laboratory Abnormalities in Phase 1
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).
Number of Participants With Laboratory Abnormalities in Phase 2
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).
Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2
Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, heart rate, weight and body surface area.
Number of Participants With Worsening QTc Results in Phase 1
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.
Number of Participants With Worsening QTc Results in Phase 2
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.
Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 1
AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau, tau=12 hours), and AUC from time 0 to last measured concentration (AUClast).
Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 2
AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau), and AUC from time 0 to last measured concentration (AUClast).
Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 1
Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 2
Systemic Clearance (CL) of Nab-paclitaxel in Phase 1
Systemic Clearance (CL) of Gemcitabine in Phase 1
Systemic Clearance (CL) of PF-03084014, Nab-P and GEM in Phase 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 2
Volume of Distribution at Steady State (Vss) for Nab-P and GEM in Phase 1
Volume of Distribution at Steady State (Vss) for PF-03084014, Nab-P and GEM in Phase 2
Plasma Decay Half-life (t1/2) for Nab-P and GEM in Phase 1
Plasma Decay Half-life (t1/2) for PF-03084014, Nab-P and GEM in Phase 2
Number of Participants With Objective Response (OR) in Phase 1
Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST).
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Number of Participants With Objective Response (OR) in Phase 2
Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST).
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Duration of Response (DR) for Phases 1 and 2
Duration of response (DR) defined as the difference in days between the first date criteria for progression occurred or the participant died due to any cause and the first date that criteria for a PR or CR were met. DR calculated as (months) = (progression/death date - first date of OR + 1) divided by 30.4. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.
1-year and 2-year OS in Phase 2
Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Progression-free Survival (PFS) in Phase 2
PFS was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first. PFS (in months) was calculated as (first event date - date of randomization +1) divided by 30.4.
Brief Pain Inventory-Short Form (BPI-sf) Score - Phase 2
BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Change From Baseline in European Quality of Life Questionnaire (EQ-5D) - Phase 2
EQ-5D: 6-item participant rated questionnaire to assess health-related quality of life in terms of a single utility score. There were 2 components: a Health State Profile and a Visual Analog Scale. Published weights are available that allow for the creation of a single summary score. Overall scores range from 0-1, with low scores representing a higher level of dysfunction.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) - Phase 2
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Full Information
NCT ID
NCT02109445
First Posted
April 2, 2014
Last Updated
December 20, 2018
Sponsor
Pfizer
Collaborators
Academic GI Cancer Consortium (AGICC)
1. Study Identification
Unique Protocol Identification Number
NCT02109445
Brief Title
Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies
Official Title
PHASE 1/2 STUDY OF PF-03084014 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated on 24JUN15 due to change in strategy of PF-03084014 development.No safety/efficacy concerns were behind the reason of trial termination
Study Start Date
September 3, 2014 (Actual)
Primary Completion Date
November 6, 2014 (Actual)
Study Completion Date
November 6, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Academic GI Cancer Consortium (AGICC)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study consists of a Phase 1b portion aimed to determine the maximum tolerated dose and the safety profile of PF-03084014 in combination with gemcitabine and nab-paclitaxel followed by a Phase 2 portion to evaluate the efficacy of the triple combination in terms of overall survival in patients with metastatic pancreatic ductal adenocarcinoma not previously treated with anticancer therapies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Cancer Pancreas
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1
Arm Type
Experimental
Arm Description
PF-03084014 in combination with gemcitabine and nab-paclitaxel
Arm Title
Phase 2 Arm A
Arm Type
Experimental
Arm Description
PF-03084014 in combination with gemcitabine and nab-paclitaxel
Arm Title
Phase 2 Arm B
Arm Type
Active Comparator
Arm Description
Gemcitabine plus nab-Paclitaxel
Intervention Type
Drug
Intervention Name(s)
PF-03084014
Intervention Description
Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Doses: 100 -150 mg BID
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.
Intervention Type
Drug
Intervention Name(s)
PF-03084014
Intervention Description
Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Phase 2 dose will be the recommended phase 2 dose defined in phase 1.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.
Primary Outcome Measure Information:
Title
Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
Description
DLT was defined as any of the following events occurring during the first cycle of treatment and considered at least possibly-related to study medication: any Grade 3 or 4 clinically-relevant non-hematologic and/or hematologic toxicity, delay of more than 2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.
Time Frame
Cycle 1 (28 days)
Title
Overall Survival (OS) in Phase 2
Description
Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame
From start of study treatment, collected every 3 months until death (up to 5 years)
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1
Description
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.
Time Frame
Baseline up to 28-35 days post last administration of study drug
Title
Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2
Description
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. Severity was graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Grade 1=mild, Grade 2=moderate, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening.
Time Frame
Baseline up to 28-35 days post last administration of study drug
Title
Number of Participants With Laboratory Abnormalities in Phase 1
Description
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).
Time Frame
Screening; Cycle 1 Days 1, 8, 15, 22; up to 28-35 days post last administration of study drug
Title
Number of Participants With Laboratory Abnormalities in Phase 2
Description
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (urea, creatinine, glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid); urinalysis (protein, blood, microscopy[if urine tested positive for blood or protein]).
Time Frame
Screening; Days 1, 8, 15 of each cycle; up to 28-35 days post last administration of study drug
Title
Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2
Description
Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, heart rate, weight and body surface area.
Time Frame
Baseline up to 28-35 days after treatment discontinuation
Title
Number of Participants With Worsening QTc Results in Phase 1
Description
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.
Time Frame
Screening, Cycle 1 Days 3 and 22, Cycles 2 and 3 Day 1, end of treatment
Title
Number of Participants With Worsening QTc Results in Phase 2
Description
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) were corrected for heart rate (QTc) using Fridericia (QTcF) and Bazett (QTcB) formulas. Any change from baseline in QTc was considered as worsening in ECG and was classified accordingly to the Common Terminology Criteria (CTC) grade. Grading was as follows: prolonged QTc of 450 to 480 milliseconds (msec)=Grade 1, 481 to 500 msec=Grade 2, more than or equal to (>=) 501 msec on at least 2 seperate ECGs=Grade 3, >=501 or more than (>) 60 msec change from baseline and Torsade de pointes or polymorphic ventricular tachycardia or signs of serious arrhythmia=Grade 4.
Time Frame
Screening, Cycle 1 Days 1 and 22, Cycles 2 and 3 Day 1, end of treatment
Title
Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 1
Description
AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau, tau=12 hours), and AUC from time 0 to last measured concentration (AUClast).
Time Frame
PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.
Title
Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 2
Description
AUC included AUC from time 0 extrapolated to infinite time (AUCinf), AUC from time 0 to end of dosing interval (AUCtau), and AUC from time 0 to last measured concentration (AUClast).
Time Frame
Cycle 1 Day 1 till end of last cycle
Title
Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 1
Time Frame
PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.
Title
Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame
Cycle 1 Day 1 till end of last cycle
Title
Systemic Clearance (CL) of Nab-paclitaxel in Phase 1
Time Frame
Cycle 1 Days 1-3, and 15-17
Title
Systemic Clearance (CL) of Gemcitabine in Phase 1
Time Frame
Cycle 1 Days 1 and 15
Title
Systemic Clearance (CL) of PF-03084014, Nab-P and GEM in Phase 2
Time Frame
Cycle 1 Day 1 till end of last cycle
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 1
Time Frame
PF-03084014: Cycle 1 Days 3, 15, 22; Day 1 of subsequent cycles; and end of treatment. nab-P: Cycle 1 Days 1-3 and 15-17. Gemcitabine: Cycle 1 Days 1 and 15.
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame
Cycle 1 Day 1 till end of last cycle
Title
Volume of Distribution at Steady State (Vss) for Nab-P and GEM in Phase 1
Time Frame
Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)
Title
Volume of Distribution at Steady State (Vss) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame
Cycle 1 Day 1 till end of last cycle
Title
Plasma Decay Half-life (t1/2) for Nab-P and GEM in Phase 1
Time Frame
Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)
Title
Plasma Decay Half-life (t1/2) for PF-03084014, Nab-P and GEM in Phase 2
Time Frame
Cycle 1 Day 1 till end of last cycle
Title
Number of Participants With Objective Response (OR) in Phase 1
Description
Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST).
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame
Screening till 28-35 days post last administration of study drug
Title
Number of Participants With Objective Response (OR) in Phase 2
Description
Number of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST).
CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame
Screening till 28-35 days post last administration of study drug
Title
Duration of Response (DR) for Phases 1 and 2
Description
Duration of response (DR) defined as the difference in days between the first date criteria for progression occurred or the participant died due to any cause and the first date that criteria for a PR or CR were met. DR calculated as (months) = (progression/death date - first date of OR + 1) divided by 30.4. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.
Time Frame
Baseline, every 8 weeks until disease progression or unacceptable toxicity (up to 5 years)
Title
1-year and 2-year OS in Phase 2
Description
Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame
From start of study treatment, collected every 3 months until death (up to 5 years)
Title
Progression-free Survival (PFS) in Phase 2
Description
PFS was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first. PFS (in months) was calculated as (first event date - date of randomization +1) divided by 30.4.
Time Frame
From start of study treatment, collected every 3 months until death (up to 5 years)
Title
Brief Pain Inventory-Short Form (BPI-sf) Score - Phase 2
Description
BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.
Time Frame
Day 1 of Cycle 1 and subsequent cycles; end of treatment
Title
Change From Baseline in European Quality of Life Questionnaire (EQ-5D) - Phase 2
Description
EQ-5D: 6-item participant rated questionnaire to assess health-related quality of life in terms of a single utility score. There were 2 components: a Health State Profile and a Visual Analog Scale. Published weights are available that allow for the creation of a single summary score. Overall scores range from 0-1, with low scores representing a higher level of dysfunction.
Time Frame
Baseline till end of treatment
Title
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) - Phase 2
Description
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Time Frame
Baseline till end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically diagnosis of metastatic ductal adenocarcinoma of the pancreas.
No prior radiotherapy, surgery chemotherapy or investigational therapy for metastatic disease. Prior adjuvant therapy with 5-FU or gemcitabine (± gemcitabine post radiation) administered as radiosensitizer allowed, provided at least 6 months have elapsed between the last dose and study registration
Tumor tissue available (Archival 6 months old or de novo biopsy)
Measurable disease as per RECIST 1.1
Performance Status (ECOG) 0 or 1
Exclusion Criteria:
Symptomatic brain metastases requiring steroids
Prior therapy with gamma secretase inhibitors or other Notch pathway inhibitor
Major surgery within 4 weeks of registration in the current study
Known hypersensitivity to gemcitabine or nab-paclitaxel or any of the excipients
Current or anticipated need for food or drugs that are strong/moderate CYP3A4 inhibitors or inducers
Diagnosis of any second malignancy within 3 years prior to registration
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
Anschutz Inpatient Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado Denver, CTO (CTRC)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Rochester Investigational Drug Pharmacy
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
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=A8641019&StudyName=%EF%82%86%0APhase%201%2F2%20Study%20Of%20Pf-03084014%20In%20Combination%20With%20Gemcitabine%20And%20Nab-paclitaxel%20In%20Patients%20With%20Previously%20Untreated%20Metastatic%20Pancreatic%20Ductal%20Adenocarcinoma%0A
Description
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Learn more about this trial
Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies
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