A Study of PF-04217903 in Patients With Advanced Cancer

实验性的：1个

药品：PF-04217903

Escalating doses of PF-04217903 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg BID to 1000 mg BID. A cycle is considered to be 21 days

Maximum Tolerated Dose (MTD)

MTD: dose level at which 1 of 6 participants experienced dose-limiting toxicity (DLT) after 21 days of treatment (Cycle 1). DLT: grade (Gr) 2 elevated creatinine, acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable),Gr >=3 non-hematological non-disease-related (NDR) toxicities (except alopecia,Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for >=7 days, febrile neutropenia, neutropenic infection, inability to deliver 80 percent of planned dose during Cycle 1 due to NDR toxicities.

Recommended Phase 2 Dose (RP2D)

Number of Participants With Dose-Limiting Toxicities (DLTs)

DLT includes Gr 2 elevated creatinine and acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable), Gr >= 3 non-hematological non-disease-related (NDR) toxicities (except alopecia, Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for >= 7 days, febrile neutropenia, neutropenic infection, inability to deliver at least 80 percent of planned dose during Cycle 1 due to NDR adverse events.

Maximum Observed Plasma Concentration (Cmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Minimum Observed Plasma Trough Concentration (Cmin) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Pre-dose Plasma Concentration (Ctrough) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration [AUC(0-last)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

Area Under the Curve From Time Zero to End of Dosing Interval [AUC(0-tau)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Area under the concentration-time profile from time zero to time tau (dosing interval), where tau is equal to 12 hours.

Accumulation Ratio (Rac) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)

Rac is obtained from AUCtau (Cycle 2 Day 1) divided by AUCtau (Cycle 1 Day 1). Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Metabolite to Parent Ratio Area Under the Curve From Time Zero to End of Dosing Interval (MRAUCtau)

Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to end of dosing interval (MRAUCtau).

Apparent Oral Clearance (CL/F) for PF-04217903

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Change From Baseline in Tumor Proliferation Using F-Fluoro-3'-Deoxy-3'-L-Fluorothymidine Positron Emission Tomography (FLT-PET) Imaging at Day 1 of Cycle 2

F-fluoro-3'-deoxy-3'-L-fluorothymidine positron emission tomography (FLT-PET) imaging was used to assess the tumor proliferation in RP2D cohorts. Results of the FLT-PET were scored according to the methods developed by the American College of Radiology Imaging Network (ACRIN).

Percentage of Participants With Objective Response (OR)

Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.