Phase 1
N=76
Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC
Metastatic Pancreatic Ductal Adenocarcinoma
Bottom Line
View on ClinicalTrials.gov: NCT02501902 ↗Enrolled (actual)
76
Serious AEs
55.3%
Results posted
Apr 2021
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicities — 0; 1; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Palbociclib (Drug); Nab-Paclitaxel (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities |
0; 1; 0; 0; 1; 1 | — |
| SECONDARY Number of Participants With Adverse Events |
3; 7; 4; 11; 11; 11 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities |
3; 7; 4; 11; 11; 11 | — |
| SECONDARY Number of Participants With Vital Signs Data Meeting Pre-specified Criteria |
1; 1; 0; 2; 2; 2 | — |
| SECONDARY Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 |
3; 5; 0; 7; 6; 5 | — |
| SECONDARY Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 |
1; 4; 0; 5; 6; 4 | — |
| SECONDARY Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 |
0; 1; 0; 3; 4; 1 | — |
| SECONDARY Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Objective Response Rate |
28.6; 6.3; 13.0 | — |
| SECONDARY Duration of Response |
NA; 7.4; 7.4 | — |
| SECONDARY Progression Free Survival |
9.1; 9.5; 1.7; 3.5; 5.5; 5.3 | — |
| SECONDARY Six-month Progression-free Survival Rate (6m-PFSR) |
66.7; 66.7; NA; 30.0; 36.4; 27.3 | — |
| SECONDARY Overall Survival (OS) |
9.8; 23.4; 3.3; 7.2; 9.9; 5.3 | — |
| SECONDARY Number of Participants With Positive p16 |
1; 2; 0; 5; 7; 6 | — |
| SECONDARY Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) |
88.3; 80.0; 68.8; 91.1; 90.5; 92.5 | — |
| SECONDARY Rb H-score Nuclear Staining |
158.3; 154.0; 108.8; 166.7; 176.0; 172.5 | — |
| SECONDARY Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) |
NA; 90.68; 57.30; 98.79; 64.55; 48.05 | — |
| SECONDARY Palbociclib Multiple Dose Time for Cmax (Tmax) |
4.93; 5.00; 3.90; 5.83; 4.50; 5.00 | — |
| SECONDARY Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) |
NA; 1497; 897.4; 1867; 1169; 767.9 | — |
| SECONDARY Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) |
NA; 43.42; 26.84; 71.82; 41.92; 22.34 | — |
| SECONDARY Palbociclib Multiple Dose Apparent Clearance (CL/F) |
NA; 66.67; 83.63; 64.52; 85.42; 97.67 | — |
| SECONDARY Nab-P Cmax |
1208; 1595; 1869; 2733; 3396; 3271 | — |
| SECONDARY Nab-P Tmax |
0.500; 1.00; 1.00; 0.567; 0.600; 0.500 | — |
| SECONDARY Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) |
2071; 3501; 3489; 4291; 4895; 4472 | — |
| SECONDARY Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) |
NA; 3851; 3780; 4157; 5387; 5132 | — |
| SECONDARY Nab-P Terminal Plasma Elimination Half-life (t1/2) |
16.95; 11.10; 12.00; 15.25; 12.85; 16.10 | — |
| SECONDARY Nab-P Clearance (CL) |
NA; 42.05; 60.94; 41.69; 37.77; 44.02 | — |
| SECONDARY Nab-P Volume of Distribution (Vz) |
NA; 709.1; 1140; 891.3; 701.6; 943.3 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02501902). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.