Clinical trial NCT02109445: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Cancer Pancreas
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Academic GI Cancer Consortium (AGICC)
First posted: 2014-04-09
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
timeFrame: Cycle 1 (28 days)
measure: Overall Survival (OS) in Phase 2
timeFrame: From start of study treatment, collected every 3 months until death (up to 5 years)
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 1
timeFrame: Baseline up to 28-35 days post last administration of study drug
measure: Number of Participants With Adverse Events (AEs) by Seriousness and Relationship to Treatment in Phase 2
timeFrame: Baseline up to 28-35 days post last administration of study drug
measure: Number of Participants With Laboratory Abnormalities in Phase 1
timeFrame: Screening; Cycle 1 Days 1, 8, 15, 22; up to 28-35 days post last administration of study drug
measure: Number of Participants With Laboratory Abnormalities in Phase 2
timeFrame: Screening; Days 1, 8, 15 of each cycle; up to 28-35 days post last administration of study drug
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Phases 1 and 2
timeFrame: Baseline up to 28-35 days after treatment discontinuation
measure: Number of Participants With Worsening QTc Results in Phase 1
timeFrame: Screening, Cycle 1 Days 3 and 22, Cycles 2 and 3 Day 1, end of treatment
measure: Number of Participants With Worsening QTc Results in Phase 2
timeFrame: Screening, Cycle 1 Days 1 and 22, Cycles 2 and 3 Day 1, end of treatment
measure: Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 1
timeFrame: 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.
measure: Area Under the Concentration-time Curve (AUC) for PF-03084014, Nab-P and Gemcitabine in Phase 2
timeFrame: Cycle 1 Day 1 till end of last cycle
measure: Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 1
timeFrame: 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.
measure: Maximum Observed Plasma Concentration (Cmax) for PF-03084014, Nab-P and GEM in Phase 2
timeFrame: Cycle 1 Day 1 till end of last cycle
measure: Systemic Clearance (CL) of Nab-paclitaxel in Phase 1
timeFrame: Cycle 1 Days 1-3, and 15-17
measure: Systemic Clearance (CL) of Gemcitabine in Phase 1
timeFrame: Cycle 1 Days 1 and 15
measure: Systemic Clearance (CL) of PF-03084014, Nab-P and GEM in Phase 2
timeFrame: Cycle 1 Day 1 till end of last cycle
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 1
timeFrame: 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.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-03084014, Nab-P and GEM in Phase 2
timeFrame: Cycle 1 Day 1 till end of last cycle
measure: Volume of Distribution at Steady State (Vss) for Nab-P and GEM in Phase 1
timeFrame: Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)
measure: Volume of Distribution at Steady State (Vss) for PF-03084014, Nab-P and GEM in Phase 2
timeFrame: Cycle 1 Day 1 till end of last cycle
measure: Plasma Decay Half-life (t1/2) for Nab-P and GEM in Phase 1
timeFrame: Cycle 1 (Days 1 and 15 for gemcitabine; Days 1-3 and 15-17 for nab-paclitaxel)
measure: Plasma Decay Half-life (t1/2) for PF-03084014, Nab-P and GEM in Phase 2
timeFrame: Cycle 1 Day 1 till end of last cycle
measure: Number of Participants With Objective Response (OR) in Phase 1
timeFrame: Screening till 28-35 days post last administration of study drug
measure: Number of Participants With Objective Response (OR) in Phase 2
timeFrame: Screening till 28-35 days post last administration of study drug
measure: Duration of Response (DR) for Phases 1 and 2
timeFrame: Baseline, every 8 weeks until disease progression or unacceptable toxicity (up to 5 years)
measure: 1-year and 2-year OS in Phase 2
timeFrame: From start of study treatment, collected every 3 months until death (up to 5 years)
measure: Progression-free Survival (PFS) in Phase 2
timeFrame: From start of study treatment, collected every 3 months until death (up to 5 years)
measure: Brief Pain Inventory-Short Form (BPI-sf) Score - Phase 2
timeFrame: Day 1 of Cycle 1 and subsequent cycles; end of treatment
measure: Change From Baseline in European Quality of Life Questionnaire (EQ-5D) - Phase 2
timeFrame: Baseline till end of treatment
measure: European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) - Phase 2
timeFrame: Baseline till end of treatment
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Anschutz Inpatient Pavilion
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Denver, CTO (CTRC)
state: Colorado
city: Rochester
country: United States
facility: University of Rochester Investigational Drug Pharmacy
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: