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CompletedNCT00666926Updated Mar 21, 2013Results posted

Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms

A Phase 1 interventional study of PF00562271 and PF00562271 in Head and Neck Neoplasm, Prostatic Neoplasm and Pancreatic Neoplasm, sponsored by Verastem, Inc.. Completed at 4 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-03-21.

Sponsored by Verastem, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
99
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Head and Neck Neoplasm
  • Prostatic Neoplasm
  • Pancreatic Neoplasm

Keywords

  • Pancreatic Neoplasm
  • Head and Neck neoplasm
  • Prostatic neoplasms; Focal Adhesion Kinase
  • Phase 1
  • Pharmacodynamics
  • FDG-PET
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 99 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Verastem, Inc. is the lead sponsor of 27 studies on the registry; 6 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Pancreatic, head and neck, and prostatic neoplasms, and patients with non-hematologic malignancies who have tumor appropriate for serial biopsy.
  • Adequate organ function, including bilirubin less than 1.5 x ULN, and [Eastern Cooperative Oncology Group] ECOG performance status of 0-2.

Exclusion criteria

Exclusion Criteria:

  • Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulants or potent CYP 3A4 inhibitors, and history of clinically significant cardiac or pulmonary disorders.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
99 participants (actual)

Study arms

  • Experimental
    1

    Drug: PF00562271

  • Experimental
    2

    Drug: PF00562271

  • Experimental
    3

    Drug: PF00562271

  • Experimental
    4

    Drug: PF00562271

Interventions

  • DrugPF00562271

    125 mg twice daily \[BID\] with food, tablet

  • DrugPF00562271

    125 mg BID with food, tablet

  • DrugPF00562271

    125 mg BID with food, tablet

  • DrugPF00562271

    125 mg BID with food, tablet

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline up to Cycle 1 Day 21 (C1.D21)

  2. 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.

    Time frame: Baseline, C1.D14

Secondary outcomes

  1. Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1

    Time frame: 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

  2. Maximum Serum Concentration (Cmax): PF-00562271 C1.D14

    Time frame: 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

  3. Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1

    Time frame: 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

  4. Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14

    Time frame: 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

  5. 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).

    Time frame: 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

  6. 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 - ∞).

    Time frame: 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

  7. 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.

    Time frame: 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

  8. 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.

    Time frame: 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

  9. Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14

    Time frame: 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

  10. Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14

    Time frame: 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

  11. 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).

    Time frame: 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

  12. Maximum Serum Concentration (Cmax): MDZ

    Time frame: 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

  13. 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.

    Time frame: 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

  14. 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 - ∞).

    Time frame: 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

  15. Time to Reach Maximum Observed Serum Concentration (Tmax): MDZ

    Time frame: 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

  16. 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.

    Time frame: 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

  17. 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.

    Time frame: 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

  18. 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.

    Time frame: Baseline up to 12 cycles (cycle=21days)

  19. 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.

    Time frame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

  20. 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.

    Time frame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

  21. 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.

    Time frame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

  22. 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.

    Time frame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

07

Results

Posted Jun 14, 2012
Limitations and caveats
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.

Participant flow

Participant flow — Overall Study
MilestonePF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 75 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Started243434413106333478
Completed0000000000000000
Not completed243434413106333478
Withdrew: Adverse event0000000002220100
Withdrew: Laboratory abnormality0000000000100001
Withdrew: Lack of efficacy0000010000010000
Withdrew: Lost to follow-up0001000000000000
Withdrew: Other24333340353263244
Withdrew: Withdrawal by subject0000000103030133
Withdrew: Death0000000000010000

Outcome measures

PrimaryNumber 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.

Time frame:
Baseline up to Cycle 1 Day 21 (C1.D21)
Reported as:
Number · participants
Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)
participantsPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 75 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)0000000000112011
PrimaryPercentage 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.

Time frame:
Baseline, C1.D14
Reported as:
Number · percentage of participants
Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)
percentage of participantsPF-00562271 125 mg BID
Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)50 (26.4 to 73.6)
SecondaryMaximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1
Time frame:
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
Reported as:
Geometric mean · nanograms per milliliter (ng/mL)
Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1
nanograms per milliliter (ng/mL)PF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QDPF-00562271 75 mg BID (Expansion Cohort)PF-00562271 100 mg BID (Expansion Cohort)PF-00562271 125 mg BID (Expansion Cohort)
Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D149.63 ± 471.13 ± 24138.8 ± 73130.1 ± 176306.1 ± 28312.9 ± 108363.2 ± 37597.6 ± 2397.3 ± 911018 ± 481236 ± 49647.2 ± 521110 ± 351528 ± 572605 ± 35421.0 ± 0474.6 ± 44747.9 ± 75
SecondaryMaximum Serum Concentration (Cmax): PF-00562271 C1.D14
Time frame:
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
Reported as:
Geometric mean · ng/mL
Maximum Serum Concentration (Cmax): PF-00562271 C1.D14
ng/mLPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Maximum Serum Concentration (Cmax): PF-00562271 C1.D1474.65 ± 80134.7 ± 55309.6 ± 58307.7 ± 145655.4 ± 721105 ± 461083 ± 841767 ± 612295 ± 742580 ± 622947 ± 623445 ± 652021 ± 173136 ± 434438 ± 49
SecondaryTime to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1
Time frame:
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
Reported as:
Median · hours
Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1
hoursPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QDPF-00562271 75 mg BID (Expansion Cohort)PF-00562271 100 mg BID (Expansion Cohort)PF-00562271 125 mg BID (Expansion Cohort)
Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D10.500 (0.500 to 0.500)1.50 (1.00 to 2.00)0.500 (0.500 to 1.00)0.500 (0.500 to 0.500)1.00 (0.500 to 2.00)1.50 (1.00 to 4.00)1.00 (1.00 to 2.00)2.00 (0.500 to 8.00)4.00 (4.00 to 4.00)2.00 (0.500 to 6.00)4.00 (0.500 to 8.00)4.00 (0.500 to 8.00)5.00 (4.00 to 6.00)4.00 (2.00 to 6.00)4.00 (2.00 to 6.00)4.00 (4.00 to 4.00)6.00 (4.00 to 8.00)4.00 (1.00 to 4.00)
SecondaryTime to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14
Time frame:
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
Reported as:
Median · hours
Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14
hoursPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D140.500 (0.500 to 0.500)1.00 (0.500 to 2.00)1.00 (1.00 to 8.00)1.50 (0.500 to 4.00)2.00 (2.00 to 12.0)1.00 (0.500 to 4.00)1.50 (1.00 to 4.00)2.00 (1.00 to 2.00)2.25 (0.000 to 12.0)3.00 (0.500 to 4.00)4.00 (0.000 to 12.0)7.00 (6.00 to 8.00)5.00 (2.00 to 8.00)2.00 (2.00 to 4.00)2.50 (0.500 to 8.00)
SecondaryArea 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).

Time frame:
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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D1
ng*hr/mLPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D181.13 ± 47233.8 ± 14348.1 ± 67295.6 ± 2131205 ± 62364 ± 1181735 ± 674407 ± 423501 ± 17110600 ± 6111900 ± 1636083 ± 13416330 ± 1220830 ± 6638600 ± 78
SecondaryArea 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 - ∞).

Time frame:
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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): PF-00562271 C0.D1, C1.D1
ng*hr/mLPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): PF-00562271 C0.D1, C1.D186.24 ± 48239.6 ± 14354.1 ± 68574.1 ± 181222 ± 62399 ± 1181759 ± 664507 ± 446588 ± 6510880 ± 715534 ± 2716101 ± 13516770 ± 1321190 ± 6537560 ± 87
SecondarySerum 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.

Time frame:
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
Reported as:
Mean · hours
Serum Decay Half-life (t 1/2): PF-00562271 C0.D1, C1.D1
hoursPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Serum Decay Half-life (t 1/2): PF-00562271 C0.D1, C1.D11.990 ± 0.608112.078 ± 0.409012.173 ± 0.387992.837 ± 1.21762.897 ± 0.533045.270 ± 1.89933.365 ± 0.884104.770 ± 0.510695.025 ± 0.629336.180 ± 2.95923.853 ± 1.43324.407 ± 1.93188.388 ± 1.93705.937 ± 1.10167.948 ± 2.7254
SecondaryApparent 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.

Time frame:
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
Reported as:
Geometric mean · milliliters per minute (mL/min)
Apparent Oral Clearance (CL/F): PF-00562271 C0. D1, C1.D1
milliliters per minute (mL/min)PF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Apparent Oral Clearance (CL/F): PF-00562271 C0. D1, C1.D1964.2 ± 48702.1 ± 17707.2 ± 68726.0 ± 18478.0 ± 6312.3 ± 118568.3 ± 66295.5 ± 44253.2 ± 64160.9 ± 71475.5 ± 553516.9 ± 120124.0 ± 13137.7 ± 6599.85 ± 87
SecondaryMinimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14
Time frame:
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
Reported as:
Geometric mean · ng/mL
Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14
ng/mLPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D140.01349 ± NA0.8059 ± 1266833998148.96 ± 8933.11 ± 1046145.8 ± 131315.3 ± 112359.8 ± 80594.5 ± 1341005 ± 1171131 ± 671253 ± 860.4111 ± NA439.6 ± 48634.7 ± 921129 ± 123
SecondaryArea Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14
Time frame:
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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14
ng*hr/mLPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14156.3 ± 53447.2 ± 1221573 ± 801476 ± 2384519 ± 848357 ± 618173 ± 7412920 ± 8620010 ± 7621120 ± 6224340 ± 7726200 ± 2224470 ± 3043140 ± 5068780 ± 71
SecondaryObserved 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).

Time frame:
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
Reported as:
Geometric mean · ratio
Observed Accumulation Ratio (Rac): PF-00562271 C1.D14
ratioPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Observed Accumulation Ratio (Rac): PF-00562271 C1.D141.864 ± 42.997 ± 264.522 ± 505.061 ± 663.899 ± 805.038 ± 1255.060 ± 993.638 ± 455.581 ± 572.967 ± 183.608 ± 491.961 ± 202.293 ± 521.118 ± 60
SecondaryMaximum Serum Concentration (Cmax): MDZ
Time frame:
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
Reported as:
Geometric mean · ng/mL
Maximum Serum Concentration (Cmax): MDZ
ng/mLPF-00562271 125 mg BID
C0.D1 (n=11)13.14 ± 47
C1.D21 (n=8)20.40 ± 31
Statistical analysis
  • PF-00562271 125 mg BID · Ratio (percent) test / reference: 155.66 · 90% CI 109.66 to 220.95Ratio of adjusted geometric means Day 21 versus Day 1. Values have been transformed from the log scale.
SecondaryArea 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.

Time frame:
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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): MDZ
ng*hr/mLPF-00562271 125 mg BID
C0.D1 (n=11)42.44 ± 53
C1.D21 (n=8)134.0 ± 22
Statistical analysis
  • PF-00562271 125 mg BID · Ratio (percent) test / reference: 315.72 · 90% CI 227.60 to 437.97Ratio of adjusted geometric means Day 21 versus Day 1. Values have been transformed from the log scale.
SecondaryArea 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 - ∞).

Time frame:
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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): MDZ
ng*hr/mLPF-00562271 125 mg BID
C0.D1 (n=11)49.79 ± 61
C1.D21 (n=5)212.3 ± 24
Statistical analysis
  • PF-00562271 125 mg BID · Ratio (percent) test / reference: 496.63 · 90% CI 206.24 to 1195.92Ratio of adjusted geometric means Day 21 versus Day 1. Values have been transformed from the log scale.
SecondaryTime to Reach Maximum Observed Serum Concentration (Tmax): MDZ
Time frame:
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
Reported as:
Median · hours
Time to Reach Maximum Observed Serum Concentration (Tmax): MDZ
hoursPF-00562271 125 mg BID
C0.D1 (n=11)0.500 (0.500 to 1.00)
C1.D21 (n=8)1.00 (0.500 to 3.00)
SecondarySerum Decay Half-life (t 1/2): MDZ

Serum decay half-life is the time measured for the serum concentration to decrease by one half.

Time frame:
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
Reported as:
Mean · hours
Serum Decay Half-life (t 1/2): MDZ
hoursPF-00562271 125 mg BID
C0.D1 (n=11)5.045 ± 1.7221
C1.D21 (n=5)7.764 ± 0.68475
SecondaryApparent 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.

Time frame:
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
Reported as:
Geometric mean · mL/hr
Apparent Oral Clearance (CL/F): MDZ
mL/hrPF-00562271 125 mg BID
C0.D1 (n=11)20090 ± 61
C1.D21 (n=5)4709 ± 24
SecondaryPercentage 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.

Time frame:
Baseline up to 12 cycles (cycle=21days)
Reported as:
Number · percentage of participants
Percentage of Participants With Best Overall Response as Measured Using the Response Evaluation Criteria in Solid Tumors (RECIST)
percentage of participantsPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 75 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Complete response0000000000000000
Partial response0000000000000000
Stable disease01222020222110131
Progressive disease23121120124153223
Indeterminate0000010104050014
SecondaryPhosphorylated 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.

Time frame:
Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

No measurements were reported for this outcome.

SecondaryPhosphorylated 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.

Time frame:
Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

No measurements were reported for this outcome.

SecondaryPhospho-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.

Time frame:
Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

No measurements were reported for this outcome.

SecondaryCaspase-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.

Time frame:
Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)

No measurements were reported for this outcome.

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PF-00562271 5 mg BID—0/2 (0%)2/2 (100%)
PF-00562271 10 mg BID—1/4 (25%)4/4 (100%)
PF-00562271 15 mg BID—0/3 (0%)3/3 (100%)
PF-00562271 25 mg BID—0/4 (0%)4/4 (100%)
PF-00562271 35 mg BID—2/3 (66.7%)3/3 (100%)
PF-00562271 45 mg BID—1/4 (25%)4/4 (100%)
PF-00562271 60 mg BID—2/4 (50%)4/4 (100%)
PF-00562271 75 mg BID—0/1 (0%)1/1 (100%)
PF-00562271 80 mg BID—0/3 (0%)3/3 (100%)
PF-00562271 100 mg BID—3/10 (30%)10/10 (100%)
PF-00562271 105 mg BID—3/6 (50%)6/6 (100%)
PF-00562271 125 mg BID—12/33 (36.4%)33/33 (100%)
PF-00562271 150 mg BID—0/3 (0%)3/3 (100%)
PF-00562271 125 mg QD—0/4 (0%)4/4 (100%)
PF-00562271 175 mg QD—0/7 (0%)7/7 (100%)
PF-00562271 225 mg QD—3/8 (37.5%)8/8 (100%)
Most frequent serious events
Showing 10 of 28
Most frequent serious events
EventPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 75 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
Gastrointestinal haemorrhageGastrointestinal disorders0/20/40/30/41/30/40/40/10/30/100/60/330/30/40/70/8
Diabetes mellitus inadequate controlMetabolism and nutrition disorders0/20/40/30/41/30/40/40/10/30/100/60/330/30/40/70/8
Mental status changesPsychiatric disorders0/20/40/30/41/30/40/40/10/30/100/60/330/30/40/70/8
Renal failure acuteRenal and urinary disorders0/20/40/30/41/30/41/40/10/30/100/60/330/30/40/70/8
Urinary retentionRenal and urinary disorders0/20/40/30/41/30/40/40/10/30/100/60/330/30/40/70/8
NauseaGastrointestinal disorders0/20/40/30/40/30/41/40/10/30/100/62/330/30/40/70/8
VomitingGastrointestinal disorders0/20/40/30/40/30/41/40/10/30/100/62/330/30/40/70/8
Back painMusculoskeletal and connective tissue disorders0/20/40/30/40/31/40/40/10/30/100/61/330/30/40/70/8
Ureteral disorderRenal and urinary disorders0/20/40/30/40/30/41/40/10/30/100/60/330/30/40/70/8
HaemoptysisRespiratory, thoracic and mediastinal disorders0/21/40/30/40/30/40/40/10/30/100/61/330/30/40/70/8
Most frequent other events
Showing 10 of 180
Most frequent other events
EventPF-00562271 5 mg BIDPF-00562271 10 mg BIDPF-00562271 15 mg BIDPF-00562271 25 mg BIDPF-00562271 35 mg BIDPF-00562271 45 mg BIDPF-00562271 60 mg BIDPF-00562271 75 mg BIDPF-00562271 80 mg BIDPF-00562271 100 mg BIDPF-00562271 105 mg BIDPF-00562271 125 mg BIDPF-00562271 150 mg BIDPF-00562271 125 mg QDPF-00562271 175 mg QDPF-00562271 225 mg QD
NauseaGastrointestinal disorders1/21/40/31/41/33/42/41/13/34/103/622/332/34/47/78/8
VomitingGastrointestinal disorders0/21/40/31/41/32/42/41/13/36/103/615/333/33/44/77/8
FatigueGeneral disorders0/22/41/34/41/32/41/41/11/33/103/616/331/34/43/76/8
Oedema peripheralGeneral disorders0/21/40/30/41/30/43/40/13/34/103/612/330/30/43/72/8
HeadacheNervous system disorders0/20/40/30/41/30/41/41/13/34/103/614/333/32/46/74/8
DiarrhoeaGastrointestinal disorders0/20/42/32/41/32/41/40/10/34/104/610/332/32/44/76/8
Urinary tract infectionInfections and infestations0/20/40/30/42/30/40/40/10/31/101/62/330/30/40/70/8
Back painMusculoskeletal and connective tissue disorders0/20/42/30/40/30/41/40/10/31/100/68/330/30/40/70/8
DizzinessNervous system disorders1/20/40/30/40/30/41/40/12/33/102/66/332/32/43/74/8
AnaemiaBlood and lymphatic system disorders0/22/40/30/40/31/40/40/10/30/101/61/330/30/41/70/8

Baseline characteristics

Age Continuous
Age Continuous(years)Entire Study Population
Mean58.7 ± 11.3
Sex: Female, Male
Sex: Female, Male(Participants)Entire Study Population
Female43
Male56
08

Study locations

4 sites
  • Pfizer Investigational Site
    Aurora, Colorado 80045, United States
  • Pfizer Investigational Site
    Nashville, Tennessee 37203, United States
  • Pfizer Investigational Site
    East Melbourne, Victoria 3002, Australia
  • Pfizer Investigational Site
    Toronto, Ontario M5G 2M9, Canada
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 21, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00666926
Lead sponsor
Verastem, Inc.
Responsible party
Sponsor
First posted
Apr 25, 2008
Start date
Dec 2005
Primary completion
Apr 2009
Completion
Apr 2009
Results posted
Jun 14, 2012
Last update
Mar 21, 2013

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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