Phase 1 N=74 Treatment

A Study Of Oral Palbociclib (PD-0332991), A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer

Neoplasms · Lymphoma, Non-Hodgkin

Bottom Line

View on ClinicalTrials.gov: NCT00141297 ↗

Enrolled (actual)

Serious AEs

28.4%

Results posted

Oct 2015

Primary outcome: Primary: Number of Participants With Dose-Limiting Toxicities (DLT) — 0; 0; 2; 0 participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: PD-0332991 (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Pfizer
Primary completion: Jul 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Dose-Limiting Toxicities (DLT)	0; 0; 2; 0; 1; 2	—
PRIMARY Maximum Administered Dose (MAD)	150; 225	—
PRIMARY Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D)	125; 200	—
PRIMARY Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature	0; 0; 1; 0; 1; 1	—
PRIMARY Number of Participants With Treatment Emergent Adverse Events Categorized by Severity	0; 2; 1; 0; 7; 1	—
PRIMARY Number of Participants With Treatment-Related Treatment Emergent Adverse Events	0; 2; 5; 3; 16; 3	—
PRIMARY Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug	0; 0; 0; 0; 0; 0	—
PRIMARY Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose	9.6; 20.7; 28.7; 45.6; 51.6; 83.8	—
PRIMARY Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose	15.9; 35.7; 58.6; 71.2; 86.2; 160.8	—
PRIMARY Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	104.0	—
PRIMARY Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect	62.0; 44.9	—
PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose	4.0; 4.0; 4.0; 4.0; 7.0; 4.0	—
PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose	4.0; 4.1; 4.0; 5.5; 4.0; 7.0	—
PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	4.2	—
PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect	7.00; 7.00	—
PRIMARY Terminal Half-life (t½ ) on Day 1: Single Dose	—	—
PRIMARY Terminal Half-life (t½ ) on Day 8: Multiple Dose	—	—
PRIMARY Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	26.5	—
PRIMARY Terminal Half-life (t½ ) on Day 1: Food Effect	—	—
PRIMARY Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose	58; 134; 199; 302; 476; 594	—
PRIMARY Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose	118; 274; 477; 560; 722; 1344	—
PRIMARY Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	3626	—
PRIMARY Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect	809; 668	—
PRIMARY Area Under the Curve From Time Zero to End of the Dosing Interval [AUC(0 to Tau)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	1863	—
PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single Dose	—	—
PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple Dose	—	—
PRIMARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect	—	—
PRIMARY Apparent Oral Clearance (CL/F) on Day 1: Single Dose	—	—
PRIMARY Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose	—	—
PRIMARY Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	86.1	—
PRIMARY Apparent Oral Clearance (CL/F) on Day 1: Food Effect	—	—
PRIMARY Apparent Volume of Distribution (Vz/F) on Day 1: Single Dose	—	—
PRIMARY Apparent Volume of Distribution (Vz/F) on Day 8: Multiple Dose	—	—
PRIMARY Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	3103	—
PRIMARY Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect	—	—
PRIMARY Accumulation Ratio (Rac) on Day 8: Multiple Dose	—	—
PRIMARY Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	2.5	—
PRIMARY Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose	—	—
PRIMARY Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose	—	—
PRIMARY Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose	0.028	—
PRIMARY Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect	—	—
PRIMARY Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose	2191; 3171	—
PRIMARY Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect	—	—
PRIMARY Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose	1.75; 1.59	—
PRIMARY Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect	—	—
PRIMARY Number of Participants With Best Response	0; 0; 0; 0; 0; 0	—
PRIMARY Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue	—	—
PRIMARY Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose	—	—
PRIMARY Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure	—	—
PRIMARY Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response	—	—

Summary

PD-0332991 may work in cancer by stopping cancer cells from multiplying. PD-0332991 is in a new class of drugs called cyclin-dependent kinase (CDK inhibitors). This research study is the first time that PD-0332991 will be given to people. PD-0332991 is taken by mouth daily.

Eligibility Criteria

Inclusion Criteria

Advanced solid tumors (excluding SCLC and retinoblastoma) or follicular of diffuse large cell non-Hodgkin's lymphoma, histologically or cytologically proven at diagnosis which is refractory to or intolerant of established therapy know to provide clinical benefit for their condition; tumors must express Rb
Adequate blood cell counts, kidney function and liver function and and ECOG score of 0, 1, or 2.
Patients may have to have tumor biopsy before and after treatment.

Exclusion Criteria

Prior stem cell or bone marrow transplant
Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse
Active or unstable cardiac disease or history of heart attack within 6 months

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00141297). 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.