Clinical trial NCT00141297: A Study Of Oral Palbociclib (PD-0332991), A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer
Official title: A Phase I Clinical, Pharmacokinetic, And Pharmacodynamic Evaluation Of 2 Schedules Of Oral PD 0332991, A Cyclin-Dependent Kinase Inhibitor, In Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lymphoma, Non-Hodgkin
Keywords: Advanced cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-09-01
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: Baseline up to 28 days
measure: Maximum Administered Dose (MAD)
timeFrame: Baseline up to 28 days
measure: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose Level (RP2D)
timeFrame: Baseline up to 28 days
measure: Number of Dose-Limiting Toxicities (DLTs) Categorized as Per the Nature
timeFrame: Baseline up to 28 days
measure: Number of Participants With Treatment Emergent Adverse Events Categorized by Severity
timeFrame: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
measure: Number of Participants With Treatment-Related Treatment Emergent Adverse Events
timeFrame: Cycle 1, Cycle 2 up to 28 days after end of treatment (up to Cycle 93)
measure: Number of Participants Who Died Due to Adverse Event on the Basis of Relatedness to Study Drug
timeFrame: Baseline up to 30 days after end of treatment (up to Cycle 93)
measure: Maximum Observed Plasma Concentration (Cmax) on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Maximum Observed Plasma Concentration (Cmax) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Maximum Observed Plasma Concentration (Cmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Maximum Observed Plasma Concentration (Cmax) on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Terminal Half-life (t½ ) on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Terminal Half-life (t½ ) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Terminal Half-life (t½) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Terminal Half-life (t½ ) on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: 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
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Apparent Oral Clearance (CL/F) on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Apparent Oral Clearance (CL/F) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Apparent Oral Clearance (CL/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Apparent Oral Clearance (CL/F) on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Apparent Volume of Distribution (Vz/F) on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Apparent Volume of Distribution (Vz/F) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Apparent Volume of Distribution (Vz/F) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Apparent Volume of Distribution (Vz/F) on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Accumulation Ratio (Rac) on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10, and 24 hours post-dose on C1D1 and C1D8
measure: Accumulation Ratio (Rac) on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Terminal Phase Rate Constant [Lambda (z)] on Day 1: Single Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 1 of Cycle 1 (C1D1)
measure: Terminal Phase Rate Constant [Lambda (z)] on Day 8: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, and 10 hours post-dose on Day 8 of Cycle 1 (C1D8)
measure: Terminal Phase Rate Constant [Lambda (z)] on Day 14/21 Dose-Corrected to 125 mg: Multiple Dose
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D21 for participants receiving 125 mg (21/28 Days) and Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D14 for participants receiving 200 mg (14/21 Days)
measure: Terminal Phase Rate Constant [Lambda (z)] on Day 1: Food Effect
timeFrame: Hour 0 (pre-dose), 1, 2, 4, 7, 10 and 24 hours post-dose on C1D1, C2D1
measure: Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Single Dose
timeFrame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
measure: Cumulative Amount of Drug Recovered Unchanged in the Urine (Ae): Food Effect
timeFrame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
measure: Percent Dose Recovered Unchanged in Urine (Percent Ae): Single Dose
timeFrame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
measure: Percent Dose Recovered Unchanged (Percent Ae) in Urine: Food Effect
timeFrame: Hour 0 (pre-dose) to 10 hours post-dose on C1D1
measure: Number of Participants With Best Response
timeFrame: Baseline up to end of treatment, assessed at C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
measure: Inhibition of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) Based on Phosphorylated Retinoblastoma (p-Rb) in Tumor Tissue
timeFrame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
measure: Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With PD 0322991 Dose
timeFrame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
measure: Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Exposure
timeFrame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
measure: Correlation of Cyclin-dependent Kinases 4 and 6 (Cdk4/6) With Tumor Response
timeFrame: Baseline, C1D1, C1D8, C1D15, C1D22, thereafter Day 1, 8, 15, and 22 of every other cycle up to end of treatment (up to Cycle 93)
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Abramson Cancer Center Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pharmacy/PCAM/West Pavillion
state: Pennsylvania
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602.
citation: Vaughn DJ, Flaherty K, Lal P, Gallagher M, O'Dwyer P, Wilner K, Chen I, Schwartz G. Treatment of growing teratoma syndrome. N Engl J Med. 2009 Jan 22;360(4):423-4. doi: 10.1056/NEJMc0808558. No abstract available.