Metastatic Pancreatic Ductal AdenocarcinomaPhase 1NCT02501902
Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
A Phase 1 study testing Palbociclib and Nab-Paclitaxel in people with Metastatic Pancreatic Ductal Adenocarcinoma, run by Pfizer at 26 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Ductal Adenocarcinoma
- What is being tested?
- Palbociclib and Nab-Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 26 sitesin 2 countries
- Study dates
- 23 Nov 2015to 27 Dec 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
26 sites in 2 countries.
26 sites in 2 countries
United States21 sites
Anschutz Cancer Pavilion
Aurora, Colorado, 80045
University of Colorado Cancer Center
Aurora, Colorado, 80045
University of Colorado Denver, CTO (CTRC)
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
Aurora, Colorado, 80045
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-1000
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Siteman Cancer Center
City of Saint Peters, Missouri, 63376
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141
UC San Diego Medical Center - La Jolla (Thornton Hospital)
La Jolla, California, 92037-0845
UC San Diego Moores Cancer Center - Investigational Drug Services
La Jolla, California, 92037-0845
UC San Diego Moores Cancer Center
La Jolla, California, 92093
University of Utah, Huntsman Cancer Hospital
Salt Lake City, Utah, 84112
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103
Scottsdale Healthcare Hospitals DBA HonorHealth
Scottsdale, Arizona, 85258
Virginia G. Piper Cancer Pharmacy
Scottsdale, Arizona, 85258
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University Infusion Center Pharmacy
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center - South County
St Louis, Missouri, 63129
Spain5 sites
Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
Barcelona, 08035
Hospital Universitario de Fuenlabrada. Unidad de Farmacia
Fuenlabrada, Madrid, 28942
Hospital Universitario Fuenlabrada
Fuenlabrada, Madrid, 28942
Hospital Universitario 12 de Octubre Servicio de Farmacia
Madrid, 28041
Hospital Universitario 12 de Octubre
Madrid, 28041
About this study
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
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.
Read the 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.
- Being tested
- Palbociclib, Nab-Paclitaxel
- Keywords
- Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Also called Ibrance
Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle.
Nab-PaclitaxelDrug
Also called Abraxane
Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
| Study group | Role | What they receive |
|---|---|---|
| Palbociclib + Nab-Paclitaxel | Experimental | 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. Receives: Drug: Palbociclib; Drug: Nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Day 1 until pre-dose Cycle 2 Day 1
Secondary outcomes (27)
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.
Measured: 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
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).
Measured: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
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.
Measured: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
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).
Measured: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Measured: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Measured: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9
Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
Measured: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
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.
Measured: From screening to 365 days from the last dose of investigational product
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.
Measured: From screening to 365 days from the last dose of investigational product
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.
Measured: From screening to 365 days from the last dose of investigational product
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.
Measured: From screening to 6 months after first dose of investigational product
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.
Measured: From screening to 365 days 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.
Measured: From Day-2 to up to 63 days from last dose of investigational product
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.
Measured: From Day-2 to up to 63 days from last dose of investigational product
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
Measured: From Day-2 to up to 63 days from last dose of investigational product
Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax)
The palbociclib multiple dose maximum plasma concentration(Cmax) was observed directly from data.
Measured: 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.
Palbociclib Multiple Dose Time for Cmax (Tmax)
The palbociclib multiple dose time for Cmax (Tmax) was observed directly from data.
Measured: 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.
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.
Measured: 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.
Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough)
The palbociclib multiple dose trough plasma concentration (Ctrough) was observed directly from data.
Measured: 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.
Palbociclib Multiple Dose Apparent Clearance (CL/F)
The palbociclib multiple dose apparent clearance (CL/F) was observed directly from data.
Measured: 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.
Nab-P Cmax
The nab-P Cmax on Cycle 1 Day -1 and Day 13 were observed directly from data.
Measured: 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.
Nab-P Tmax
The nab-P Tmax on Day -1 and Day 13 were observed directly from data.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
Nab-P Clearance (CL)
The nab-P clearance on Day -1 and Day 13 were observed directly from data.
Measured: 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.
Nab-P Volume of Distribution (Vz)
The nab-P on Day -1 and Day 13 were observed directly from data.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study start23 Nov 2015
- Primary completion10 Oct 2018
- Study completion27 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02501902
- Sponsor's protocol ID
- A5481059
- Other IDs
- 2015-001307-31, 2015
- Status last verified
- Mar 2021
- First submitted
- 14 Jul 2015
- Last updated
- 6 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: 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.
Publications
Hidalgo M, Garcia-Carbonero R, Lim KH, Messersmith WA, Garrido-Laguna I, Borazanci E, Lowy AM, Medina Rodriguez L, Laheru D, Salvador-Barbero B, Malumbres M, Shields DJ, Grossman JE, Huang X, Tammaro M, Martini JF, Yu Y, Kern K, Macarulla T. A Preclinical and Phase Ib Study of Palbociclib plus Nab-Paclitaxel in Patients with Metastatic Adenocarcinoma of the Pancreas. Cancer Res Commun. 2022 Nov 2;2(11):1326-1333. doi: 10.1158/2767-9764.CRC-22-0072. eCollection 2022 Nov.
PubMed 36970055
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02501902
- Acronym / sponsor ID
- A5481059
- Keywords
- Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Celgene
- Study start
- 23 Nov 2015 (actual)
- Primary completion
- 10 Oct 2018 (actual)
- Study completion
- 27 Dec 2018 (actual)
- First posted
- 17 Jul 2015 (estimated)
- Results
- Posted 6 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Palbociclib + Nab-Paclitaxel | Experimental | Drug: Palbociclib, Drug: Nab-PaclitaxelPalbociclib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PalbociclibAlso: IbrancePalbociclib oral dosing on Days 1 to 21 of each 28-day cycle. | Drug | Palbociclib + Nab-Paclitaxel |
| Nab-PaclitaxelAlso: AbraxaneNab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles. | Drug | Palbociclib + Nab-Paclitaxel |
Primary outcome
Number of Participants With Dose Limiting Toxicities
Time frame: From Day 1 until pre-dose Cycle 2 Day 1
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.
27 secondary outcomes
Number of Participants With Adverse Events
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
Number of Participants With Laboratory Abnormalities
Time frame: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
Time frame: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9
Time frame: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9
Time frame: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9
Time frame: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9
Time frame: From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).
Objective Response Rate
Time frame: From screening to 365 days from the last dose of investigational product
Duration of Response
Time frame: From screening to 365 days from the last dose of investigational product
Progression Free Survival
Time frame: From screening to 365 days from the last dose of investigational product
Six-month Progression-free Survival Rate (6m-PFSR)
Time frame: From screening to 6 months after first dose of investigational product
Overall Survival (OS)
Time frame: From screening to 365 days from the last dose of investigational product
Number of Participants With Positive p16
Time frame: From Day-2 to up to 63 days from last dose of investigational product
Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining)
Time frame: From Day-2 to up to 63 days from last dose of investigational product
Rb H-score Nuclear Staining
Time frame: From Day-2 to up to 63 days from last dose of investigational product
Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax)
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.
Palbociclib Multiple Dose Time for Cmax (Tmax)
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.
Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ)
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.
Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough)
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.
Palbociclib Multiple Dose Apparent Clearance (CL/F)
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.
Nab-P Cmax
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.
Nab-P Tmax
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.
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast)
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.
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
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.
Nab-P Terminal Plasma Elimination Half-life (t1/2)
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.
Nab-P Clearance (CL)
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.
Nab-P Volume of Distribution (Vz)
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36970055Hidalgo M, Garcia-Carbonero R, Lim KH, Messersmith WA, Garrido-Laguna I, Borazanci E, Lowy AM, Medina Rodriguez L, Laheru D, Salvador-Barbero B, Malumbres M, Shields DJ, Grossman JE, Huang X, Tammaro M, Martini JF, Yu Y, Kern K, Macarulla T. A Preclinical and Phase Ib Study of Palbociclib plus Nab-Paclitaxel in Patients with Metastatic Adenocarcinoma of the Pancreas. Cancer Res Commun. 2022 Nov 2;2(11):1326-1333. doi: 10.1158/2767-9764.CRC-22-0072. eCollection 2022 Nov.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
26 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Palbociclib and Nab-Paclitaxel in people with Metastatic Pancreatic Ductal Adenocarcinoma, run by Pfizer at 26 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (time frame: From Day 1 until pre-dose Cycle 2 Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02501902, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.