A Study Of PF-03084014 In Japanese Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine the recommended Phase 2 dose for PF-03084014 single-agent administration in Japanese patients with advanced solid tumors. Pharmacokinetics and the overall safety profile of PF-03084014 will also be evaluated.

Official Title
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Phase 1 Study Of Pf-03084014 To Evaluate Safety And Pharmacokinetics In Japanese Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: PF-03084014


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of advanced solid tumors that is resistant to standard therapy or for which no standard therapy is available. Age ≥18 years. ECOG Performance Status (PS) must be 0 or 1. Adequate Bone Marrow Function Adequate Renal Function Adequate Liver Function Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 Exclusion Criteria: Patients with known brain metastases Major surgery within 4 weeks of starting study treatment Radiation therapy within 2 weeks of starting study treatment Systemic anti cancer therapy within 2 weeks (4 weeks for antibody) of starting study treatment Previous high dose chemotherapy requiring stem cell rescue Prior irradiation to >25% of the bone marrow Prior treatment with a Notch signal inhibitor Known malabsorption syndrome or other condition that may impair absorption of study medication Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism Current use or anticipated need for known strong and/or moderate CYP3A4 inhibitors Current use or anticipated need for known strong CYP3A4 inducers

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-03084014<br> | Drug: PF-03084014<br>* gamma-secretase inhibitor, formulated in tablets for oral administration containing 10 mg, 50 mg and 100 mg. Patient will receive 80 mg, 100 mg or 150 mg twice daily of PF-03084014 with continuous dosing schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First-cycle Dose Limiting Toxicities |  | during the first 28 days from the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| QTc interval |  | from the first dose to the last dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Plasma Decay Half-Life (t1/2) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Apparent Oral Clearance (CL/F) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Apparent Volume of Distribution at steady state (Vss/F) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Minimum Observed Plasma Trough Concentration (Cmin) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Average Serum Concentration at steady state (Cav) |  | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose | 
| Accumulation Ratio (Rac) |  | 0, 0.5, 1, 2, 4, 8 hours post-dose on Day 1 and Day 21 |