A Study Of PF-04554878 In Patients With Advanced Non-Hematologic Malignancies

Study Overview
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Brief Summary
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Phase 1 safety, pharmacokinetics, and pharmacodynamics trial of the focal adhesion kinase (FAK) inhibitor PF-04554878 in patients with advanced non-hematologic malignancies, including patients with malignancies appropriate for serial biopsy. Screening consists of medical history, physical examination ECOG performance status, blood draws, a pregnancy test for female patients of childbearing potential, a FDG-PET and tumor imaging. Treatment consists of PF-04554878 pills 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 activities.

Official Title
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A Phase 1, Open-Label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of PF-04554878 In Patients With Advanced Non-Hematologic Malignancies

Conditions
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Cancer

Intervention / Treatment
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* Drug: PF-04554878


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced non-hematologic malignancies. Adequate organ function, including bilirubin less than 1.5 x ULN, and ECOG (Eastern Cooperative Oncology Group) performance status of 0-2. Exclusion Criteria: Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulants or potent CYP 2C8 inhibitors, and history of clinically significant cardiac or pulmonary disorders

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Dose escalation study with Expansion Cohorts at RP2D and Schedule | Drug: PF-04554878<br>* Oral pills at increasing dose twice daily, 21 day cycle, continuous treatment schedule until progression of disease, unacceptable toxicity, or patient request. Some patients will undergo serial biopsy and/or FDG-PET imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Phase 2 Dose |  | 18 months | 
| Overall safety profile of PF-04554878, including Dose-Limiting Toxicity (DLT) |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor metabolic response |  | 18 months | 
| PF-04554878 pharmacokinetic (PK) parameters and Midazolam PK parameters |  | 18 months | 
| FAK-related biomarkers in tumor biopsies and blood |  | 18 months | 
| Molecular profiling (genomics data) based on the optional studies with whole blood and/or tumor samples |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Focal Adhesion Kinase; Advanced Non-Hematologic Malignancies