Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC



Status:Completed
Healthy:No
Age Range:18 - Any
Updated:3/28/2019
Start Date:November 23, 2015
End Date:December 27, 2018

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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.

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.

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.
We found this trial at
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Baltimore, Maryland 21231
410-955-6190
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The name Johns Hopkins has become synonymous...
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330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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Aurora, Colorado 80045
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Aurora, Colorado 80045
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Creve Coeur, Missouri 63141
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3855 Health Sciences Dr,
La Jolla, California 92093
(858) 822-6100
UC San Diego Moores Cancer Center Established in 1978, UC San Diego Moores Cancer Center...
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Saint Louis, Missouri 63129
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Saint Louis, Missouri 63110
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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150 Entranceway Drive
Saint Peters, Missouri 63376
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San Diego, California 92103
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Scottsdale, Arizona 85258
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