Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]PF00299804
PF-00299804 · 9 trials · 8 indications
Percentage of participants with best OR of confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) relative to total number of evaluable participants for response. CR defined as disappearance of all target/non-target lesions. PR defined as at least a 30 percent (%) decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR and PR) were those that persisted on a follow-up imaging assessment greater than or equal to (≥)4 weeks after the initial objective documentation of response.
PFS: Time in weeks from randomization to date of objective disease progression or death due to any cause, whichever occurred first. PFS was calculated as (first event date or last known event-free date \[if the event date unavailable\] minus the date of randomization plus 1) divided by 7. Objective progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LDs) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
BOR:best response recorded from treatment start until disease progression as per Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response: disappearance of all lesions. Partial Response (PR):greater than or equal to (\>=)30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):\>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease:neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
The highest dose at which less than (\<) 33 percent (%) of participants experienced dose-limiting toxicities (DLT) was to be designated as the maximum tolerated dose (MTD) as well as the RP2D. DLT was defined as any of the following events: Grade 3/4 (severe or life-threatening/ disabling adverse event \[AE\]) nausea, vomiting, or diarrhea (despite the use of adequate/maximal medical intervention and/or prophylaxis); Grade greater than or equal to (\>=) 3 (severe or life-threatening/disabling AE or death related to AE) non-hematological toxicity; delayed (which delayed scheduled treatment for \>14 days) recovery from toxicity related to treatment with PF-00299804; Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells per cubic millimeter \[cells/mm\^3\] for 5 or more consecutive days or febrile neutropenia \[fever \>=38.5 degrees Celsius with ANC \<1000 cells/mm\^3\]); and Grade 4 thrombocytopenia (\<25,000 cells/mm\^3) or bleeding which required platelet transfusion.
PFS4m was defined as percent chance of being event free (event defined as progressive disease \[PD\] or death due to any cause, whichever occurred first) at 4 months. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.
Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.
Dextrorphan is an active metabolite of dextromethorphan.
Dextrorphan is an active metabolite of dextromethorphan.
Dextrorphan is an active metabolite of dextromethorphan.
Dextrorphan is an active metabolite of dextromethorphan.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.
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. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
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. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day -3 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day -3.
The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day 7 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day 7.
| Arm | Type | Description |
|---|---|---|
| A | EXPERIMENTAL | - |
| B | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | descriptive: adenocarcinoma histology |
| 2 | EXPERIMENTAL | descriptive: non-adenocarcinoma histology |
| Treatment arm | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| PF-00299804 | DRUG | 45 mg by continuous oral dosing |
| Erlotinib | DRUG | Continuous oral dosing at 150 mg daily. |
| [14C]PF00299804 | DRUG | Single 45 mg oral dose of radiolabelled PF-00299804 |
Inclusion Criteria: * Recurrent or metastatic Squamous Cell Cancer of the Head and Neck; * Measurable disease; * Eastern Cooperative Oncology Group (ECOG) 0-1 in Stage 1 = first 23 patients; * Eastern Cooperative Oncology Group (ECOG) 0-2 in Stage 2 = 33 patients; Exclusion Criteria: * prior ther...
PF-00299804 is an investigational oral small molecule developed by Pfizer, Inc. (NYSE: PFE) for the treatment of cancer. It has been studied in advanced malignant solid tumors, non-small cell lung cancer, and head and neck neoplasms. It is not approved and remains in clinical development.
PF-00299804 has been studied in non-small cell lung cancer, including a Phase 2 trial comparing oral PF-00299804 with oral erlotinib in patients whose disease progressed after one or two prior chemotherapy regimens. It is investigational and has not been approved for any indication.
PF-00299804 is developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer sponsored the clinical trials evaluating the compound in solid tumors, non-small cell lung cancer, and head and neck cancer.
PF-00299804 has been tested in Phase 1 and Phase 2 clinical trials. Three completed studies are registered, including two Phase 1 trials and two Phase 2 trials, and no trials are currently active. The drug is investigational and has not received FDA approval.
Registered trials include NCT01034748, a radiolabeled mass balance study in healthy male volunteers; NCT00783328, a Phase 1 study in Japanese patients with advanced solid tumors; NCT00769067, a Phase 2 trial versus erlotinib in non-small cell lung cancer; and NCT00768664, a Phase 2 trial in head and neck cancer. All are completed.
Yes. PF-00299804 is also written as PF00299804, and [14C]PF00299804 refers to the carbon-14 radiolabeled form used in a mass balance study. These names refer to the same Pfizer compound.