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Trial record 1 of 1 for:    NCT02501902
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Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC

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ClinicalTrials.gov Identifier: NCT02501902
Recruitment Status : Completed
First Posted : July 17, 2015
Last Update Posted : May 30, 2019
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 14, 2015
First Posted Date  ICMJE July 17, 2015
Last Update Posted Date May 30, 2019
Actual Study Start Date  ICMJE November 2015
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: Baseline up to 28 days ]
DLT defined as any of the following events occurring during the first 28 days of palbociclib and considered at least possibly-related to study medication: Grade 4 neutropenia lasting > 4 days; Febrile neutropenia (defined as neutropenia Grade ≥3 [ANC <1000 cells/mm3] and a body temperature ≥38.5°C) requiring antibiotic or antifungal treatment; Any Grade 4 thrombocytopenia (<25,000/mm3 or <25.0 x 109/L); Grade 3 toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea); Any palbociclib treatment delay of greater than 7 days; Omission of at least 2 of the 3 weekly doses of nab-P.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Palbociclib Area Under the Curve (AUC) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
  • Nab-Paclitaxel Area Under the Curve (AUC) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
  • Palbociclib Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2, Days 1 and 15: Pre-dose. ]
  • Nab-Paclitaxel Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
  • Palbociclib Plasma Decay Half-Life (t1/2) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Nab-Paclitaxel Plasma Decay Half-Life (t1/2) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Palbociclib Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
  • Nab-Paclitaxel Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
  • Palbociclib Apparent Oral Clearance (CL/F) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Nab-Paclitaxel Apparent Oral Clearance (CL/F) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Palbociclib Volume of Distribution at Steady State (Vss) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
  • Nab-Paclitaxel Volume of Distribution at Steady State (Vss) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
  • Palbociclib Systemic Clearance (CL) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Nab-Paclitaxel Systemic Clearance (CL) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Blood CA 19-9 Levels [ Time Frame: Day 1 of each cycle for approximately 12 months ]
    CA 19-9 measures the level of tumor-associated antigens found in the blood. CA 19-9 antigens are foreign substances released by pancreatic tumor cells.
  • Objective Response Rate - Percentage of Participants With Complete or Partial Response [ Time Frame: Baseline until approximately 12 months. ]
    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Measured from baseline until disease progression or death due to any cause.
  • Duration of Response (DR) [ Time Frame: Baseline until approximately 12 months. ]
    Time in weeks/months from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response is calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7 (or 30.44 if in months). DR was calculated for the subgroup of participants with a confirmed objective tumor response. DR is usually categorized by the median with its 95% Confidence Interval (CI), range and 25% and 75% percentiles.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline until approximately 12 months. ]
    The period from study entry until disease progression, death or date of last contact.
  • Six-Month PFS Rate [ Time Frame: When last patient has been enrolled for 6 months. ]
    Percentage of patients who do not have progressive disease after 6 months on study.
  • Overall Survival (OS) [ Time Frame: Baseline until approximately 13 months. ]
    Time in weeks or months from the start of study treatment to date of death due to any cause. OS is calculated as (the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 7 or 30.44 if in months.
  • Tumor Tissue Biomarkers (p16 and Rb1 expression) [ Time Frame: Baseline and end of study treatment (approximately 9 months). ]
    Tumor tissue biomarkers (p16 and Rb1 expression by immunohistochemistry)
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
  • Palbociclib Area Under the Curve (AUC) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
  • Nab-Paclitaxel Area Under the Curve (AUC) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
  • Palbociclib Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2, Days 1 and 15: Pre-dose. ]
  • Nab-Paclitaxel Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
  • Palbociclib Plasma Decay Half-Life (t1/2) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Nab-Paclitaxel Plasma Decay Half-Life (t1/2) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Palbociclib Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
  • Nab-Paclitaxel Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
  • Palbociclib Apparent Oral Clearance (CL/F) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Nab-Paclitaxel Apparent Oral Clearance (CL/F) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Palbociclib Volume of Distribution at Steady State (Vss) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
  • Nab-Paclitaxel Volume of Distribution at Steady State (Vss) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
  • Palbociclib Systemic Clearance (CL) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 2, 4, 6, 8, and 24 hours post dose; Cycle 2 Days 1 and 15: Pre-dose. ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Nab-Paclitaxel Systemic Clearance (CL) [ Time Frame: Cycle 1 Day -2 and 13: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, and 48 hours post dose. Cycle 2 Days 1 and 15: Pre-dose. ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Blood CA 19-9 Levels [ Time Frame: Day 1 of each cycle for approximately 12 months ]
    CA 19-9 measures the level of tumor-associated antigens found in the blood. CA 19-9 antigens are foreign substances released by pancreatic tumor cells.
  • Objective Response Rate - Percentage of Participants With Complete or Partial Response [ Time Frame: Baseline until approxmately 12 months. ]
    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Measured from baseline until disease progression or death due to any cause.
  • Duration of Response (DR) [ Time Frame: Baseline until approximately 12 months. ]
    Time in weeks/months from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response is calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7 (or 30.44 if in months). DR was calculated for the subgroup of participants with a confirmed objective tumor response. DR is usually categorized by the median with its 95% Confidence Interval (CI), range and 25% and 75% percentiles.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline until approximately 12 months. ]
    The period from study entry until disease progression, death or date of last contact.
  • Six-Month PFS Rate [ Time Frame: When last patient has been enrolled for 6 months. ]
    Percentage of patients who do not have progressive disease after 6 months on study.
  • Overall Survival (OS) [ Time Frame: Baseline until approximately 13 months. ]
    Time in weeks or months from the start of study treatment to date of death due to any cause. OS is calculated as (the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 7 or 30.44 if in months.
  • Tumor Tissue Biomarkers (p16 and Rb1 expression) [ Time Frame: Baseline and end of study treatment (approximately 9 months). ]
    Tumor tissue biomarkers (p16 and Rb1 expression by immunohistochemistry)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Ductal Adenocarcinoma
Intervention  ICMJE
  • Drug: Palbociclib
    Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle.
    Other Name: Ibrance
  • Drug: Nab-Paclitaxel
    Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
    Other Name: Abraxane
Study Arms  ICMJE Experimental: Palbociclib + Nab-Paclitaxel
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.
Interventions:
  • Drug: Palbociclib
  • Drug: Nab-Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 29, 2019)
76
Original Estimated Enrollment  ICMJE
 (submitted: July 15, 2015)
60
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT02501902
Other Study ID Numbers  ICMJE A5481059
2015-001307-31 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Celgene
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP