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Phase 1 safety, pharmacokinetics, and pharmacodynamics trial of the focal adhesion kinase (FAK) inhibitor PF-00562271 in patients with positive Positron Emission Tomography [PET] scans due to advanced non-hematologic malignancies, including pancreatic, head and neck, and prostatic neoplasms, and patients with other malignancies appropriate for serial biopsy. Screening consists of a Fluorodeoxyglucose Positron Emission Tomography [FDG-PET] and tumor imaging, medical history, physical examination, Eastern Cooperative Oncology Group [ECOG] performance status, blood draws, a pregnancy test for female patients of childbearing potential. Treatment consists of PF00562271 tablets continued until progression of disease, unacceptable toxicity, or patient request. Evaluations for bioactivity are measured by serial FDG-PET and blood tests for biomarkers related to FAK and PYK2 kinase activities.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
| |
| 2 | Experimental |
| |
| 3 | Experimental |
| |
| 4 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF00562271 | Drug | 125 mg twice daily [BID] with food, tablet |
| |
| PF00562271 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | At least possibly attributable to study treatment (Tx): Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for >7 days or Gr 3 febrile neutropenia (ANC <1000/mm^3, fever ≥38 degrees Celsius; Gr 4 thrombocytopenia (platelets <25,000 cells/mm^3); Gr ≥3 non-hematologic toxicity despite adequate medical intervention; Gr ≥3 confirmed prolonged QTc interval (>500 milliseconds [msec]); confirmed cardiac troponin I ≥99 percentile of reference range; Tx related toxicities with failure to receive ≥18 days Tx in 21-day cycle or inability to resume current dose level ≤14 days. | Baseline up to Cycle 1 Day 21 (C1.D21) |
| Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET) | Metabolic response demonstrated in any tumor reduction of ≥15% in tumor FDG standardized uptake value (SUV) in Cycle 1; based on the recommendations of the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Participant must have had a baseline PET with at least 1 tumor lesion demonstrating an FDG SUV of ≥5. | Baseline, C1.D14 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1 | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 morning (am) dose | |
| Maximum Serum Concentration (Cmax): PF-00562271 C1.D14 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Aurora | Colorado | 80045 | United States | ||
| Pfizer Investigational Site |
Not provided
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Expansion cohort (E1 or E2): participants were to be those enrolled at maximum tolerated dose level. E1: to have advanced disease likely to possess functional aberrations of pathways for tumorigenesis (represent focal adhesion kinase [FAK] expression). E2: to have disease characteristics associated with FAK expression and agree to repeat biopsies.
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-00562271 5 mg BID | PF-00562271 administered as 5 milligrams (mg) orally (PO) twice a day (BID) without food (w/o food: no food within 2 hours prior to dosing) (escalation cohort). |
| FG001 | PF-00562271 10 mg BID | PF-00562271 administered as 10 mg PO BID w/o food (escalation cohort). |
| FG002 | PF-00562271 15 mg BID | PF-00562271 administered as 15 mg PO BID w/o food (escalation cohort). |
| FG003 | PF-00562271 25 mg BID | PF-00562271 administered as 25 mg PO BID w/o food (escalation cohort). |
| FG004 | PF-00562271 35 mg BID | PF-00562271 administered as 35 mg PO BID w/o food (escalation cohort). |
| FG005 | PF-00562271 45 mg BID | PF-00562271 administered as 45 mg PO BID w/o food (escalation cohort). |
| FG006 | PF-00562271 60 mg BID | PF-00562271 administered as 60 mg PO BID w/o food (escalation cohort). |
| FG007 | PF-00562271 75 mg BID | PF-00562271 administered as 75 mg PO BID with food (w/food: regular meal 200 to 800 calories) (expansion cohort). As of July 2008, participants newly enrolled to the expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration w/food): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Participant who was not able to titrate higher than 75 mg BID was reported in the 75 mg BID expansion cohort. |
| FG008 | PF-00562271 80 mg BID | PF-00562271 administered as 80 mg PO BID w/o food (escalation cohort). |
| FG009 | PF-00562271 100 mg BID | PF-00562271 administered as 100 mg BID w/food (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration w/food): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Participants who were not able to titrate higher than 100 mg BID were reported in the 100 mg BID cohort. Escalation and expansion cohorts were combined for reporting. |
| FG010 | PF-00562271 105 mg BID | PF-00562271 administered as 105 mg PO BID w/o food (escalation cohort). |
| FG011 | PF-00562271 125 mg BID | PF-00562271 administered as 125 mg PO BID w/food (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration w/food): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Additional participants were to be enrolled to the expansion cohort at the maximum tolerated dose (MTD) 125 mg BID (expansion cohort [E1 or E2]); E1 cohort United States (US) participants received Midazolam (MDZ) syrup 2 mg per milliliter (mg/mL) as a single PO dose 24 hours prior to first PF-00562271 dose (w/o food 2 hours prior to and after MDZ dosing) and on Cycle 1, Day 21 (C1.D21) simultaneously with PF-00562271 dosing (w/food). E1 participants outside the US and E2 participants were not dosed with MDZ. Escalation and expansion cohorts were combined for reporting. |
| FG012 | PF-00562271 150 mg BID | PF-00562271 administered as 150 mg PO BID w/food (escalation cohort). |
| FG013 | PF-00562271 125 mg QD | PF-00562271 administered as 125 mg PO once a day (QD) w/o food (escalation cohort). |
| FG014 | PF-00562271 175 mg QD | PF-00562271 administered as 175 mg PO QD w/o food (escalation cohort). |
| FG015 | PF-00562271 225 mg QD | PF-00562271 administered as 225 mg PO QD w/o food (escalation cohort). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | PF-00562271 dose escalation administered as 5 mg PO BID up to 150 mg PO BID or 125 mg PO QD up to 225 mg PO QD. Participants in the PF-00562271125 mg BID US E1 cohort administered MDZ 2 mg/mL as a single dose on C1.D1 and C1.D21 prior to PF-00562271 dosing. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | At least possibly attributable to study treatment (Tx): Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for >7 days or Gr 3 febrile neutropenia (ANC <1000/mm^3, fever ≥38 degrees Celsius; Gr 4 thrombocytopenia (platelets <25,000 cells/mm^3); Gr ≥3 non-hematologic toxicity despite adequate medical intervention; Gr ≥3 confirmed prolonged QTc interval (>500 milliseconds [msec]); confirmed cardiac troponin I ≥99 percentile of reference range; Tx related toxicities with failure to receive ≥18 days Tx in 21-day cycle or inability to resume current dose level ≤14 days. | Safety analysis set: All enrolled participants who started treatment. | Posted | Number | participants | Baseline up to Cycle 1 Day 21 (C1.D21) |
|
Treatment-emergent adverse events are recorded from the time of first dose of study treatment up to 28 days after last dose of study treatment or until start of new anti-cancer treatment, whichever occurs first.
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-00562271 5 mg BID | PF-00562271 administered as 5 milligrams (mg) orally (PO) twice a day (BID) without food (w/o food: no food within 2 hours prior to dosing) (escalation cohort). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
PET and RECIST Response Analysis Sets as defined in Protocol Amendment 3 dated 20Mar2007 are reported in Basic Results per the revised definitions in Statistical Analysis Plan version 2 dated 11Apr2008.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mitchell Keegan | Verastem, Inc. | 617-252-9300 | mkeegan@verastem.com |
Not provided
| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D011471 | Prostatic Neoplasms |
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
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| ID | Term |
|---|---|
| C573150 | PF-00562271 |
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| Drug |
125 mg BID with food, tablet |
|
| PF00562271 | Drug | 125 mg BID with food, tablet |
|
| PF00562271 | Drug | 125 mg BID with food, tablet |
|
| Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
| Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1 | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
| Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14 | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D1 | Area under the serum concentration time-curve from zero to the last measured concentration; nanograms multiplied by hours per milliliters (ng*hr/mL). | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): PF-00562271 C0.D1, C1.D1 | AUCinf = area under the serum concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
| Serum Decay Half-life (t 1/2): PF-00562271 C0.D1, C1.D1 | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
| Apparent Oral Clearance (CL/F): PF-00562271 C0. D1, C1.D1 | 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. | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
| Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14 | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
| Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14 | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
| Observed Accumulation Ratio (Rac): PF-00562271 C1.D14 | Rac was the ratio of the Day 14 AUC0-tau (0 hour to last dose interval) and AUC during the corresponding time period after the lead-in dose (AUCtau C1.D14/AUCtau C0.D1). | Escalation (Esc) cohort: C0.D1: 0 hr, and 0.5, 1, 2, 4, 6, 7,12 hrs post dose; Expansion (Exp) cohort: C0:D1: 0 hr, and 1, 2, 4, 8 hrs post dose; Esc and Exp cohorts: C1.D14 0 hour, and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
| Maximum Serum Concentration (Cmax): MDZ | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): MDZ | Area under the serum concentration time-curve from zero to the last measured concentration. | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): MDZ | AUCinf = area under the serum concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
| Time to Reach Maximum Observed Serum Concentration (Tmax): MDZ | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
| Serum Decay Half-life (t 1/2): MDZ | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
| Apparent Oral Clearance (CL/F): MDZ | 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. | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
| Percentage of Participants With Best Overall Response as Measured Using the Response Evaluation Criteria in Solid Tumors (RECIST) | Best response recorded from start of treatment (Tx) until disease progression. Complete response: disappearance of all target lesions. Partial response: ≥30% decrease in sum of longest dimensions (LD) of target lesions referencing baseline sum LD. Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions. Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start. | Baseline up to 12 cycles (cycle=21days) |
| Phosphorylated Focal Adhesion Kinase (pFAK) | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; FAK is overexpressed in a variety of human cancers. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose and on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
| Phosphorylated Mitogen Activated Pathway Kinase (pMAPK) | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; MAPK regulates activities of several transcription factors. A defect in MAPK pathway leads to uncontrolled cell growth. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose and on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
| Phospho-SRC (pSRC) | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; SRC proto-oncogenes are regulators of growth and differentiation of eukaryotic cells and are implicated in development of human tumors. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose; on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
| Caspase-3 | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose and on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
| Nashville |
| Tennessee |
| 37203 |
| United States |
| Pfizer Investigational Site | East Melbourne | Victoria | 3002 | Australia |
| Pfizer Investigational Site | Toronto | Ontario | M5G 2M9 | Canada |
| Laboratory abnormality |
|
| Lack of Efficacy |
|
| Lost to Follow-up |
|
| Other |
|
| Withdrawal by Subject |
|
| Death |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | PF-00562271 10 mg BID | PF-00562271 administered as 10 mg PO BID w/o food (escalation cohort). |
| OG002 | PF-00562271 15 mg BID | PF-00562271 administered as 15 mg PO BID w/o food (escalation cohort). |
| OG003 | PF-00562271 25 mg BID | PF-00562271 administered as 25 mg PO BID w/o food (escalation cohort). |
| OG004 | PF-00562271 35 mg BID | PF-00562271 administered as 35 mg PO BID w/o food (escalation cohort). |
| OG005 | PF-00562271 45 mg BID | PF-00562271 administered as 45 mg PO BID w/o food (escalation cohort). |
| OG006 | PF-00562271 60 mg BID | PF-00562271 administered as 60 mg PO BID w/o food (escalation cohort). |
| OG007 | PF-00562271 75 mg BID | PF-00562271 administered as 75 mg PO BID with food (w/food: regular meal 200 to 800 calories) (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Participant who was not able to titrate higher than 75 mg BID was reported in the 75 mg BID cohort. |
| OG008 | PF-00562271 80 mg BID | PF-00562271 administered as 80 mg PO BID w/o food (escalation cohort). |
| OG009 | PF-00562271 100 mg BID | PF-00562271 administered as 100 mg BID w/food (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Participants who were not able to titrate higher than 100 mg BID were reported in the 100 mg BID cohort. |
| OG010 | PF-00562271 105 mg BID | PF-00562271 administered as 105 mg PO BID w/o food (escalation cohort). |
| OG011 | PF-00562271 125 mg BID | PF-00562271 administered as 125 mg PO BID w/food (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Additional participants were to be enrolled to the expansion cohort at the maximum tolerated dose (MTD) 125 mg BID (expansion cohort [E1 or E2]); E1 cohort United States (US) participants received Midazolam (MDZ) syrup 2 mg per milliliter (mg/mL) as a single PO dose 24 hours prior to first PF-00562271 dose (w/o food 2 hours prior to and after MDZ dosing) and on Cycle 1, Day 21 simultaneously with PF-00562271 dosing (w/food). E1 participants outside the US and E2 participants were not dosed with MDZ. |
| OG012 | PF-00562271 150 mg BID | PF-00562271 administered as 150 mg PO BID w/food (escalation cohort). |
| OG013 | PF-00562271 125 mg QD | PF-00562271 administered as 125 mg PO once a day (QD) w/o food (escalation cohort). |
| OG014 | PF-00562271 175 mg QD | PF-00562271 administered as 175 mg PO QD w/o food (escalation cohort). |
| OG015 | PF-00562271 225 mg QD | PF-00562271 administered as 225 mg PO QD w/o food (escalation cohort). |
|
|
| Primary | Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET) | Metabolic response demonstrated in any tumor reduction of ≥15% in tumor FDG standardized uptake value (SUV) in Cycle 1; based on the recommendations of the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Participant must have had a baseline PET with at least 1 tumor lesion demonstrating an FDG SUV of ≥5. | Participants in the 125 mg BID expansion cohort with at least 1 dose of study treatment, at least 1 lesion with an SUV ≥5 at baseline, and an on-study PET assessment C1.D14 (Day 13 up to Day 17). | Posted | Number | 90% Confidence Interval | percentage of participants | Baseline, C1.D14 |
|
|
|
| Secondary | Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1 | Pharmacokinetic (PK) parameter analysis set: all participants with at least 1 dose of study treatment and at least 1 of the PK parameters of interest estimated in at least 1 treatment period. Escalation cohorts: Cycle 0 48 hours post dose timepoint = C1.D1. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 morning (am) dose |
|
|
|
| Secondary | Maximum Serum Concentration (Cmax): PF-00562271 C1.D14 | PK parameter analysis set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
|
|
|
| Secondary | Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1 | PK parameter analysis set. Escalation cohorts: Cycle 0 48 hours post dose timepoint = C1.D1. | Posted | Median | Full Range | hours | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
|
|
|
| Secondary | Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14 | PK parameter analysis set | Posted | Median | Full Range | hours | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
|
|
|
| Secondary | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D1 | Area under the serum concentration time-curve from zero to the last measured concentration; nanograms multiplied by hours per milliliters (ng*hr/mL). | PK parameter analysis set. Escalation cohorts: Cycle 0 48 hours post dose timepoint = C1.D1. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
|
|
|
| Secondary | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): PF-00562271 C0.D1, C1.D1 | AUCinf = area under the serum concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | PK parameter analysis set. Escalation cohorts: Cycle 0 48 hours post dose timepoint = C1.D1. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
|
|
|
| Secondary | Serum Decay Half-life (t 1/2): PF-00562271 C0.D1, C1.D1 | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | PK parameter analysis set. Escalation cohorts: Cycle 0 48 hours post dose timepoint = C1.D1. | Posted | Mean | Standard Deviation | hours | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
|
|
|
| Secondary | Apparent Oral Clearance (CL/F): PF-00562271 C0. D1, C1.D1 | 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. | PK parameter analysis set. Escalation cohorts: Cycle 0 48 hours post dose timepoint = C1.D1. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliters per minute (mL/min) | Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose |
|
|
|
| Secondary | Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14 | PK parameter analysis set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
|
|
|
| Secondary | Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14 | PK parameter analysis set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
|
|
|
| Secondary | Observed Accumulation Ratio (Rac): PF-00562271 C1.D14 | Rac was the ratio of the Day 14 AUC0-tau (0 hour to last dose interval) and AUC during the corresponding time period after the lead-in dose (AUCtau C1.D14/AUCtau C0.D1). | PK parameter analysis set | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Escalation (Esc) cohort: C0.D1: 0 hr, and 0.5, 1, 2, 4, 6, 7,12 hrs post dose; Expansion (Exp) cohort: C0:D1: 0 hr, and 1, 2, 4, 8 hrs post dose; Esc and Exp cohorts: C1.D14 0 hour, and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose |
|
|
|
| Secondary | Maximum Serum Concentration (Cmax): MDZ | N=participants in the PK parameter analysis set who received MDZ dosing prior to PF-00562271 in the 125 mg BID cohort; (n)=number of participants with analyzable data at observation. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
|
|
|
|
| Secondary | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): MDZ | Area under the serum concentration time-curve from zero to the last measured concentration. | N=participants in the PK parameter analysis set who received MDZ dosing prior to PF-00562271 in the 125 mg BID cohort; (n)=number of participants with analyzable data at observation. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
|
|
|
|
| Secondary | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): MDZ | AUCinf = area under the serum concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | N=participants in the PK parameter analysis set who received MDZ dosing prior to PF-00562271 in the 125 mg BID cohort; (n)=number of participants with analyzable data at observation. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
|
|
|
|
| Secondary | Time to Reach Maximum Observed Serum Concentration (Tmax): MDZ | N=participants in the PK parameter analysis set who received MDZ dosing prior to PF-00562271 in the 125 mg BID cohort; (n)=number of participants with analyzable data at observation. | Posted | Median | Full Range | hours | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
|
|
|
| Secondary | Serum Decay Half-life (t 1/2): MDZ | Serum decay half-life is the time measured for the serum concentration to decrease by one half. | N=participants in the PK parameter analysis set who received MDZ dosing prior to PF-00562271 in the 125 mg BID cohort; (n)=number of participants with analyzable data at observation. | Posted | Mean | Standard Deviation | hours | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
|
|
|
| Secondary | Apparent Oral Clearance (CL/F): MDZ | 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. | N=participants in the PK parameter analysis set who received MDZ dosing prior to PF-00562271 in the 125 mg BID cohort; (n)=number of participants with analyzable data at observation. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hr | C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose |
|
|
|
| Secondary | Percentage of Participants With Best Overall Response as Measured Using the Response Evaluation Criteria in Solid Tumors (RECIST) | Best response recorded from start of treatment (Tx) until disease progression. Complete response: disappearance of all target lesions. Partial response: ≥30% decrease in sum of longest dimensions (LD) of target lesions referencing baseline sum LD. Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions. Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start. | RECIST response analysis set: all enrolled participants who had an adequate baseline tumor assessment, measureable disease and who started treatment. N=number of participants with evaluable data at observation. | Posted | Number | percentage of participants | Baseline up to 12 cycles (cycle=21days) |
|
|
|
| Secondary | Phosphorylated Focal Adhesion Kinase (pFAK) | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; FAK is overexpressed in a variety of human cancers. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose and on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Data was not summarized as samples were processed and analyzed later than 3 days after collection and thus the data were considered unusable. | Posted | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
|
|
| Secondary | Phosphorylated Mitogen Activated Pathway Kinase (pMAPK) | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; MAPK regulates activities of several transcription factors. A defect in MAPK pathway leads to uncontrolled cell growth. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose and on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Data was not summarized as samples were processed and analyzed later than 3 days after collection and thus the data were considered unusable. | Posted | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
|
|
| Secondary | Phospho-SRC (pSRC) | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; SRC proto-oncogenes are regulators of growth and differentiation of eukaryotic cells and are implicated in development of human tumors. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose; on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Data was not summarized as samples were processed and analyzed later than 3 days after collection and thus the data were considered unusable. | Posted | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
|
|
| Secondary | Caspase-3 | Analysis of tumor specimens to assess FAK-related biomarkers for potential predictors of response markers to PF-00562271; sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. For dose escalation cohorts and expansion cohort E1, pre-treatment tumor biopsy collected between Day -28 and first PF-00562271 dose and on-treatment tumor biopsy collected 2 to 8 hours after PF-00562271 dose during Cycle 1 between day 12 and 16. In addition, up to 10 participants in cohort E2 were to be enrolled for serial biopsies. | Data was not summarized as samples were processed and analyzed later than 3 days after collection and thus the data were considered unusable. | Posted | Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days) |
|
|
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | PF-00562271 10 mg BID | PF-00562271 administered as 10 mg PO BID w/o food (escalation cohort). | 1 | 4 | 4 | 4 |
| EG002 | PF-00562271 15 mg BID | PF-00562271 administered as 15 mg PO BID w/o food (escalation cohort). | 0 | 3 | 3 | 3 |
| EG003 | PF-00562271 25 mg BID | PF-00562271 administered as 25 mg PO BID w/o food (escalation cohort). | 0 | 4 | 4 | 4 |
| EG004 | PF-00562271 35 mg BID | PF-00562271 administered as 35 mg PO BID w/o food (escalation cohort). | 2 | 3 | 3 | 3 |
| EG005 | PF-00562271 45 mg BID | PF-00562271 administered as 45 mg PO BID w/o food (escalation cohort). | 1 | 4 | 4 | 4 |
| EG006 | PF-00562271 60 mg BID | PF-00562271 administered as 60 mg PO BID w/o food (escalation cohort). | 2 | 4 | 4 | 4 |
| EG007 | PF-00562271 75 mg BID | PF-00562271 administered as 75 mg PO BID with food (w/food: regular meal 200 to 800 calories) (expansion cohort). As of July 2008, participants newly enrolled to the expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration w/food): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Participant who was not able to titrate higher than 75 mg BID was reported in the 75 mg BID expansion cohort. | 0 | 1 | 1 | 1 |
| EG008 | PF-00562271 80 mg BID | PF-00562271 administered as 80 mg PO BID w/o food (escalation cohort). | 0 | 3 | 3 | 3 |
| EG009 | PF-00562271 100 mg BID | PF-00562271 administered as 100 mg BID w/food (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration w/food): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Participants who were not able to titrate higher than 100 mg BID were reported in the 100 mg BID cohort. Escalation and expansion cohorts were combined for reporting. | 3 | 10 | 10 | 10 |
| EG010 | PF-00562271 105 mg BID | PF-00562271 administered as 105 mg PO BID w/o food (escalation cohort). | 3 | 6 | 6 | 6 |
| EG011 | PF-00562271 125 mg BID | PF-00562271 administered as 125 mg PO BID w/food (escalation cohort). As of July 2008, participants newly enrolled to expansion cohort or who restarted treatment after dose delay associated with adverse event(s) were dosed according to intra-participant escalation (up-titration w/food): 75 mg BID week 1; 100 mg BID week 2; 125 mg BID week 3. Additional participants were to be enrolled to the expansion cohort at the maximum tolerated dose (MTD) 125 mg BID (expansion cohort [E1 or E2]); E1 cohort United States (US) participants received Midazolam (MDZ) syrup 2 mg per milliliter (mg/mL) as a single PO dose 24 hours prior to first PF-00562271 dose (w/o food 2 hours prior to and after MDZ dosing) and on Cycle 1, Day 21 simultaneously with PF-00562271 dosing (w/food). E1 participants outside the US and E2 participants were not dosed with MDZ. Escalation and expansion cohorts were combined for reporting. | 12 | 33 | 33 | 33 |
| EG012 | PF-00562271 150 mg BID | PF-00562271 administered as 150 mg PO BID w/food (escalation cohort). | 0 | 3 | 3 | 3 |
| EG013 | PF-00562271 125 mg QD | PF-00562271 administered as 125 mg PO once a day (QD) w/o food (escalation cohort). | 0 | 4 | 4 | 4 |
| EG014 | PF-00562271 175 mg QD | PF-00562271 administered as 175 mg PO QD w/o food (escalation cohort). | 0 | 7 | 7 | 7 |
| EG015 | PF-00562271 225 mg QD | PF-00562271 administered as 225 mg PO QD w/o food (escalation cohort). | 3 | 8 | 8 | 8 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ureteral disorder | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Microcytic anaemia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysacusis | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
|
| Endocrine disorder | Endocrine disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Breath odour | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lip swelling | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oral discomfort | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Facial pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Local swelling | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Localised oedema | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oedema | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Vaginal infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Viral diarrhoea | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Periorbital haematoma | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood amylase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood prolactin increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Cardiac murmur | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Metabolic alkalosis | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Osteoporotic fracture | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Amnesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Carpal tunnel syndrome | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Breast disorder | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Red man syndrome | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Corrective lens user | Social circumstances | MedDRA (12.1) | Systematic Assessment |
|
| Tooth extraction | Surgical and medical procedures | MedDRA (12.1) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Subclavian vein thrombosis | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D004067 | Digestive System Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| Partial response |
|
| Stable disease |
|
| Progressive disease |
|
| Indeterminate |
|