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Phase 1 N=99 Treatment

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

Head and Neck Neoplasm · Prostatic Neoplasm · Pancreatic Neoplasm

Enrolled (actual)
99
Serious AEs
27.3%
Results posted
Jun 2012
Primary outcome: Primary: Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) — 0; 0; 0; 0 participants

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
PF00562271 (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Verastem, Inc.
Primary completion
Apr 2009

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)
0; 0; 0; 0; 0; 0
PRIMARY
Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)
50
SECONDARY
Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1
49.63; 71.13; 138.8; 130.1; 306.1; 312.9
SECONDARY
Maximum Serum Concentration (Cmax): PF-00562271 C1.D14
74.65; 134.7; 309.6; 307.7; 655.4; 1105
SECONDARY
Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1
0.500; 1.50; 0.500; 0.500; 1.00; 1.50
SECONDARY
Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14
0.500; 1.00; 1.00; 1.50; 2.00; 1.00
SECONDARY
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D1
81.13; 233.8; 348.1; 295.6; 1205; 2364
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): PF-00562271 C0.D1, C1.D1
86.24; 239.6; 354.1; 574.1; 1222; 2399
SECONDARY
Serum Decay Half-life (t 1/2): PF-00562271 C0.D1, C1.D1
1.990; 2.078; 2.173; 2.837; 2.897; 5.270
SECONDARY
Apparent Oral Clearance (CL/F): PF-00562271 C0. D1, C1.D1
964.2; 702.1; 707.2; 726.0; 478.0; 312.3
SECONDARY
Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14
0.01349; 0.8059; 48.96; 33.11; 145.8; 315.3
SECONDARY
Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14
156.3; 447.2; 1573; 1476; 4519; 8357
SECONDARY
Observed Accumulation Ratio (Rac): PF-00562271 C1.D14
1.864; 2.997; 4.522; 5.061; 3.899; 5.038
SECONDARY
Maximum Serum Concentration (Cmax): MDZ
13.14; 20.40
SECONDARY
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): MDZ
42.44; 134.0
SECONDARY
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): MDZ
49.79; 212.3
SECONDARY
Time to Reach Maximum Observed Serum Concentration (Tmax): MDZ
0.500; 1.00
SECONDARY
Serum Decay Half-life (t 1/2): MDZ
5.045; 7.764
SECONDARY
Apparent Oral Clearance (CL/F): MDZ
20090; 4709
SECONDARY
Percentage of Participants With Best Overall Response as Measured Using the Response Evaluation Criteria in Solid Tumors (RECIST)
0; 0; 0; 0; 0; 0
SECONDARY
Phosphorylated Focal Adhesion Kinase (pFAK)
SECONDARY
Phosphorylated Mitogen Activated Pathway Kinase (pMAPK)
SECONDARY
Phospho-SRC (pSRC)
SECONDARY
Caspase-3

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.

Eligibility Criteria

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

  • Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulants or potent CYP 3A4 inhibitors, and history of clinically significant cardiac or pulmonary disorders.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00666926). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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