Back to resultsDose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
Primary Purpose
Metastatic Pancreatic Ductal Adenocarcinoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Palbociclib
Nab-Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Ductal Adenocarcinoma focused on measuring Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma.
- Availability of a tumor tissue specimen. If no archived tumor tissue is available, then a de novo biopsy is required for patient participation.
- Karnofsky Performance Status 70 or greater.
- Adequate Bone Marrow, Renal, and Liver Function.
Exclusion Criteria:
- Prior treatment with a CDK 4/6 inhibitor.
- Prior treatment with nab-P for the treatment of metastatic disease.
- Patients with known CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
- Diagnosis of any other malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
- QTc >480 msec, or family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
- Uncontrolled electrolyte disorders.
- Cardiac or pulmonary disorders within 6 months of enrollment.
- Known human immunodeficiency virus infection.
- History of interstitial lung disease or pneumonitis.
- Other severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-P.
- Difficulty swallowing capsules or requirement for a feeding tube.
- Previous high-dose chemotherapy requiring stem cell rescue.
- Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant.
- Active inflammatory or other gastrointestinal disease,
- Active bleeding disorder in the past 6 months.
- Patients treated within the last 7 days prior to the start of IP with strong/moderate CYP3A4 inhibitors, strong/moderate CYP3A4 inducers, CYP2C8 inhibitors, strong/moderate CYP2C8 inducers, or drugs that are known to prolong the QT interval.
Sites / Locations
- Scottsdale Healthcare Hospitals DBA HonorHealth
- Virginia G. Piper Cancer Pharmacy
- UC San Diego Medical Center - La Jolla (Thornton Hospital)
- UC San Diego Moores Cancer Center - Investigational Drug Services
- UC San Diego Moores Cancer Center
- UC San Diego Medical Center - Hillcrest
- Anschutz Cancer Pavilion
- University of Colorado Cancer Center
- University of Colorado Denver, CTO (CTRC)
- University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
- University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Beth Israel Deaconess Medical Center
- Siteman Cancer Center - West County
- Barnes-Jewish Hospital
- Washington University Infusion Center Pharmacy
- Washington University School of Medicine
- Siteman Cancer Center - South County
- Siteman Cancer Center
- University of Utah, Huntsman Cancer Hospital
- University of Utah, Huntsman Cancer Institute
- Hospital Universitario de Fuenlabrada. Unidad de Farmacia
- Hospital Universitario Fuenlabrada
- Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
- Hospital Universitario 12 de Octubre Servicio de Farmacia
- Hospital Universitario 12 de Octubre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Palbociclib + Nab-Paclitaxel
Arm Description
Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle. Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
Outcomes
Primary Outcome Measures
Number of Participants With Dose Limiting Toxicities
Adverse events (AEs) considered as dose limiting toxicities (DLTs) included: hematologic: Grade 4 neutropenia lasting >4 days; Febrile neutropenia (defined as neutropenia Grade>=3 [absolute neutrophil count {ANC}<1000 cells/cubic millimeter {mm^3}] and a body temperature >=38.5 [degrees centigrade]℃) requiring antibiotic or antifungal treatment; any Grade 4 thrombocytopenia (<25000/mm^3 or 25.0*10^9/[liter]L). Non-hematologic: Grade >=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea). Any AE that caused a palbociclib treatment interruption of greater than 7 consecutive days or caused any combination of interruption/reduction for >=14 days. Any AE that caused omission or reduction of at least 2 of the 3 weekly doses of nab-P.
Secondary Outcome Measures
Number of Participants With Adverse Events
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of investigational product. Disease progression was not considered a treatment emergent AE unless the participant died of disease prior to 28 days after discontinuation of treatment. Treatment emergent AEs with cause possibly, probably or definitely related to treatment, as judged by the investigator, were defined as treatment-related AEs. AEs were graded by investigator according to CTCAE v4.03.
Number of Participants With Laboratory Abnormalities
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to NCI CTCAE v4.0 were summarized: hematology (anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils, platelets and white blood cells) and chemistry laboratory tests (alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, creatinine, hypercalcemia, hyperglocemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase).
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Suggest text: Vital signs categorical summary included: 1)SBP>150mmHg or DBP>100mmHg; 2)SBP>200mmHg or DBP>110mmHg; 3)SBP increase >=20 and <40mmHg; 4)SBP increase >=40 and <60mmHg; 5)SBP increase>=60mmHg; 6)DBP increase >=10 and <20mmHg; 7)DBP increase >=20 and <30mmHg; 8)DBP increase >=30mmHg; 9)pulse rate>120bpm; 10)pulse rate<50bpm.
Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9
Carbohydrate antigen 19-9 (Ca19-9) is a clinical pharmacodynamic (PD) marker associated with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Objective Response Rate
Percentage of participants who achieved objective response (OR) based on investigator assessment is presented. OR is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Objective response rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR relative to all anti-tumor evaluable participants.
Duration of Response
The duration of response was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. Disease progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm.
Progression Free Survival
The progression free survival (PFS) was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression as per RECIST v1.1 or death due to any cause in the absence of documented progression disease, whichever occurred first.
Six-month Progression-free Survival Rate (6m-PFSR)
6m-PFS was defined as PFS status (progression free and alive, or not) at Month 6. It was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.
Overall Survival (OS)
OS was defined as the time from the date of first dose to the date of death due to any cause. Following the end of treatment visit, survival status was collected in all participants every month until 12 months (365 days) had elapsed from the last dose of investigational product.
Number of Participants With Positive p16
p16 is a tumor suppressor protein which plays an important role in cell cycle regulation. The analysis of biomarker p16 expression might aid in the identification of patient subpopulations most likely to benefit from treatment. The results from p16 expression testing by immunohistochemistry (IHC) was used for sensitivity analyses. (a) and (b) :p16 cutoff utilizing the optimal cut point identified by the ORC analysis for the OS (a) or PFS (b) and the p16 positive tumor cells.
Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining)
Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses.
Rb H-score Nuclear Staining
Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3*percentage of strongly staining nuclei + 2*percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving the range of 0 to 300
Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax)
The palbociclib multiple dose maximum plasma concentration(Cmax) was observed directly from data.
Palbociclib Multiple Dose Time for Cmax (Tmax)
The palbociclib multiple dose time for Cmax (Tmax) was observed directly from data.
Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ)
The palbociclib area under the plasma concentration-time curve for dosing interval τ (AUCτ) was observed directly from data.
Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough)
The palbociclib multiple dose trough plasma concentration (Ctrough) was observed directly from data.
Palbociclib Multiple Dose Apparent Clearance (CL/F)
The palbociclib multiple dose apparent clearance (CL/F) was observed directly from data.
Nab-P Cmax
The nab-P Cmax on Cycle 1 Day -1 and Day 13 were observed directly from data.
Nab-P Tmax
The nab-P Tmax on Day -1 and Day 13 were observed directly from data.
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast)
The nab-P area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) on Day -1 and Day 13 were observed directly from data.
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
The nab-P area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUCinf) on Day -1 and Day 13 observed directly from data.
Nab-P Terminal Plasma Elimination Half-life (t1/2)
The nab-P t1/2 on Day -1 and Day 13 were observed directly from data.
Nab-P Clearance (CL)
The nab-P clearance on Day -1 and Day 13 were observed directly from data.
Nab-P Volume of Distribution (Vz)
The nab-P on Day -1 and Day 13 were observed directly from data.
Full Information
NCT ID
NCT02501902
First Posted
July 14, 2015
Last Updated
March 10, 2021
Sponsor
Pfizer
Collaborators
Celgene
1. Study Identification
Unique Protocol Identification Number
NCT02501902
Brief Title
Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
Official Title
AN OPEN-LABEL PHASE IB STUDY OF PALBOCICLIB (ORAL CDK 4/6 INHIBITOR) PLUS ABRAXANE (REGISTERED) (NAB-PACLITAXEL) IN PATIENTS WITH METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
November 23, 2015 (Actual)
Primary Completion Date
October 10, 2018 (Actual)
Study Completion Date
December 27, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1, open label, multi center, multiple dose, dose escalation, safety, pharmacokinetic and pharmacodynamic study of palbociclib in combination with nab-P, in sequential cohorts of adult patients with mPDAC, with MTD expansion cohort(s). Approximately 30-60 patients are expected to be enrolled in the overall study.
Detailed Description
The study has 2 parts:
• Part A (Dose-Escalation Cohorts): Consecutive cohorts of patients will receive escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles, in order to estimate the MTD(s) of the combination. The starting doses will be 75 mg palbociclib, and 100 mg/m2 nab-P. The observation period for dose-limiting toxicities (DLTs) will be from Day 1 to Day 28. Pharmacokinetic (PK) and pharmacodynamic (PD) properties of palbociclib and nab-P will also be assessed. Up to approximately 30 patients will be enrolled. The criteria for dose escalation will be based on a modified toxicity probability interval (mTPI) method.
• Part B [MTD Expansion Cohort(s)]: When the MTD(s) of palbociclib plus nab-P has been estimated with confidence, enrollment will proceed into 1 or 2 MTD expansion cohort(s) of up to 20 patients each at the MTD(s). The objective of the MTD expansion cohort(s) will be to provide additional information on safety, tolerability, biomarkers, PD activity, and PK/PD relationship for the combination regimen in order to determine the RP2D. The MTD expansion cohort(s) will only enroll patients who have not received previous treatment for their metastatic disease in order to evaluate preliminary activity of the combination in the target patient population.
All patients (in Part A and B) will receive nab-P intravenously once weekly for 3 weeks out of each 28-day cycle. Palbociclib oral dosing will be once daily on Days 1-21 of each 28-day cycle. To allow for PK evaluation of nab-P administered alone, nab-P will be administered on Day -2 for Cycle 1 only. Subsequent cycles will administer both nab-P and palbociclib on Day 1. Alternate dosing schedules for palbociclib may be explored based on emerging PK, PD, and safety data.
Patients will be treated as long as they are clinically benefiting from investigational product without unacceptable toxicity, objective disease progression, or withdrawal of consent. A modified visit schedule will be implemented for patients who are on investigational product for more than 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Ductal Adenocarcinoma
Keywords
Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Palbociclib + Nab-Paclitaxel
Arm Type
Experimental
Arm Description
Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle. Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Other Intervention Name(s)
Ibrance
Intervention Description
Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Nab-Paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities
Description
Adverse events (AEs) considered as dose limiting toxicities (DLTs) included: hematologic: Grade 4 neutropenia lasting >4 days; Febrile neutropenia (defined as neutropenia Grade>=3 [absolute neutrophil count {ANC}<1000 cells/cubic millimeter {mm^3}] and a body temperature >=38.5 [degrees centigrade]℃) requiring antibiotic or antifungal treatment; any Grade 4 thrombocytopenia (<25000/mm^3 or 25.0*10^9/[liter]L). Non-hematologic: Grade >=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea). Any AE that caused a palbociclib treatment interruption of greater than 7 consecutive days or caused any combination of interruption/reduction for >=14 days. Any AE that caused omission or reduction of at least 2 of the 3 weekly doses of nab-P.
Time Frame
From Day 1 until pre-dose Cycle 2 Day 1
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of investigational product. Disease progression was not considered a treatment emergent AE unless the participant died of disease prior to 28 days after discontinuation of treatment. Treatment emergent AEs with cause possibly, probably or definitely related to treatment, as judged by the investigator, were defined as treatment-related AEs. AEs were graded by investigator according to CTCAE v4.03.
Time Frame
From the signing of informed consent up to 56 days after the last administration of the investigational product, or 365 days from the first dose of investigational product, whichever is later
Title
Number of Participants With Laboratory Abnormalities
Description
The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to NCI CTCAE v4.0 were summarized: hematology (anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils, platelets and white blood cells) and chemistry laboratory tests (alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, creatinine, hypercalcemia, hyperglocemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase).
Time Frame
From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Title
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
Description
Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Suggest text: Vital signs categorical summary included: 1)SBP>150mmHg or DBP>100mmHg; 2)SBP>200mmHg or DBP>110mmHg; 3)SBP increase >=20 and <40mmHg; 4)SBP increase >=40 and <60mmHg; 5)SBP increase>=60mmHg; 6)DBP increase >=10 and <20mmHg; 7)DBP increase >=20 and <30mmHg; 8)DBP increase >=30mmHg; 9)pulse rate>120bpm; 10)pulse rate<50bpm.
Time Frame
From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Title
Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9
Description
Carbohydrate antigen 19-9 (Ca19-9) is a clinical pharmacodynamic (PD) marker associated with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Time Frame
From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Title
Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9
Description
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Time Frame
From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Title
Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9
Description
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Time Frame
From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Title
Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9
Description
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Time Frame
From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Title
Objective Response Rate
Description
Percentage of participants who achieved objective response (OR) based on investigator assessment is presented. OR is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Objective response rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR relative to all anti-tumor evaluable participants.
Time Frame
From screening to 365 days from the last dose of investigational product
Title
Duration of Response
Description
The duration of response was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. Disease progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm.
Time Frame
From screening to 365 days from the last dose of investigational product
Title
Progression Free Survival
Description
The progression free survival (PFS) was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression as per RECIST v1.1 or death due to any cause in the absence of documented progression disease, whichever occurred first.
Time Frame
From screening to 365 days from the last dose of investigational product
Title
Six-month Progression-free Survival Rate (6m-PFSR)
Description
6m-PFS was defined as PFS status (progression free and alive, or not) at Month 6. It was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.
Time Frame
From screening to 6 months after first dose of investigational product
Title
Overall Survival (OS)
Description
OS was defined as the time from the date of first dose to the date of death due to any cause. Following the end of treatment visit, survival status was collected in all participants every month until 12 months (365 days) had elapsed from the last dose of investigational product.
Time Frame
From screening to 365 days from the last dose of investigational product
Title
Number of Participants With Positive p16
Description
p16 is a tumor suppressor protein which plays an important role in cell cycle regulation. The analysis of biomarker p16 expression might aid in the identification of patient subpopulations most likely to benefit from treatment. The results from p16 expression testing by immunohistochemistry (IHC) was used for sensitivity analyses. (a) and (b) :p16 cutoff utilizing the optimal cut point identified by the ORC analysis for the OS (a) or PFS (b) and the p16 positive tumor cells.
Time Frame
From Day-2 to up to 63 days from last dose of investigational product
Title
Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining)
Description
Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses.
Time Frame
From Day-2 to up to 63 days from last dose of investigational product
Title
Rb H-score Nuclear Staining
Description
Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3*percentage of strongly staining nuclei + 2*percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving the range of 0 to 300
Time Frame
From Day-2 to up to 63 days from last dose of investigational product
Title
Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax)
Description
The palbociclib multiple dose maximum plasma concentration(Cmax) was observed directly from data.
Time Frame
Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.
Title
Palbociclib Multiple Dose Time for Cmax (Tmax)
Description
The palbociclib multiple dose time for Cmax (Tmax) was observed directly from data.
Time Frame
Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.
Title
Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ)
Description
The palbociclib area under the plasma concentration-time curve for dosing interval τ (AUCτ) was observed directly from data.
Time Frame
Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.
Title
Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough)
Description
The palbociclib multiple dose trough plasma concentration (Ctrough) was observed directly from data.
Time Frame
Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.
Title
Palbociclib Multiple Dose Apparent Clearance (CL/F)
Description
The palbociclib multiple dose apparent clearance (CL/F) was observed directly from data.
Time Frame
Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.
Title
Nab-P Cmax
Description
The nab-P Cmax on Cycle 1 Day -1 and Day 13 were observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
Title
Nab-P Tmax
Description
The nab-P Tmax on Day -1 and Day 13 were observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
Title
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast)
Description
The nab-P area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) on Day -1 and Day 13 were observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
Title
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
Description
The nab-P area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUCinf) on Day -1 and Day 13 observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
Title
Nab-P Terminal Plasma Elimination Half-life (t1/2)
Description
The nab-P t1/2 on Day -1 and Day 13 were observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
Title
Nab-P Clearance (CL)
Description
The nab-P clearance on Day -1 and Day 13 were observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
Title
Nab-P Volume of Distribution (Vz)
Description
The nab-P on Day -1 and Day 13 were observed directly from data.
Time Frame
Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma.
Availability of a tumor tissue specimen. If no archived tumor tissue is available, then a de novo biopsy is required for patient participation.
Karnofsky Performance Status 70 or greater.
Adequate Bone Marrow, Renal, and Liver Function.
Exclusion Criteria:
Prior treatment with a CDK 4/6 inhibitor.
Prior treatment with nab-P for the treatment of metastatic disease.
Patients with known CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
Diagnosis of any other malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
QTc >480 msec, or family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
Uncontrolled electrolyte disorders.
Cardiac or pulmonary disorders within 6 months of enrollment.
Known human immunodeficiency virus infection.
History of interstitial lung disease or pneumonitis.
Other severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-P.
Difficulty swallowing capsules or requirement for a feeding tube.
Previous high-dose chemotherapy requiring stem cell rescue.
Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant.
Active inflammatory or other gastrointestinal disease,
Active bleeding disorder in the past 6 months.
Patients treated within the last 7 days prior to the start of IP with strong/moderate CYP3A4 inhibitors, strong/moderate CYP3A4 inducers, CYP2C8 inhibitors, strong/moderate CYP2C8 inducers, or drugs that are known to prolong the QT interval.
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
Scottsdale Healthcare Hospitals DBA HonorHealth
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Virginia G. Piper Cancer Pharmacy
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
UC San Diego Medical Center - La Jolla (Thornton Hospital)
City
La Jolla
State/Province
California
ZIP/Postal Code
92037-0845
Country
United States
Facility Name
UC San Diego Moores Cancer Center - Investigational Drug Services
City
La Jolla
State/Province
California
ZIP/Postal Code
92037-0845
Country
United States
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
UC San Diego Medical Center - Hillcrest
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Anschutz Cancer 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 Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-1000
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Siteman Cancer Center - West County
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University Infusion Center Pharmacy
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center - South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
Siteman Cancer Center
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Facility Name
University of Utah, Huntsman Cancer Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Utah, Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Hospital Universitario de Fuenlabrada. Unidad de Farmacia
City
Fuenlabrada
State/Province
Madrid
ZIP/Postal Code
28942
Country
Spain
Facility Name
Hospital Universitario Fuenlabrada
City
Fuenlabrada
State/Province
Madrid
ZIP/Postal Code
28942
Country
Spain
Facility Name
Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre Servicio de Farmacia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
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.
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A5481059&StudyName=An%20Open-label%20Phase%20Ib%20Study%20Of%20Palbociclib%20%28oral%20Cdk%204%2F6%20Inhibitor%29%20Plus%20Abraxane%20%28registered%29%20%28nab-paclitaxel%29%20In%20Patients%20With%20Metastatic%20Pancreatic%20Ductal%20Adenocarcinoma
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
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