Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
Condition: Metastatic Pancreatic Ductal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Palbociclib; Nab-Paclitaxel
Intervention 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 MeSH terms: Paclitaxel; Palbociclib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,

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.
    

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.