Advanced Solid Tumors
Conditions
Brief summary
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.
Interventions
DRUGPF-03084014
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
Sponsors
Pfizer
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| First-cycle Dose Limiting Toxicities | during the first 28 days from the first dose |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Maximum Observed Plasma Concentration (Cmax) | 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 |
| Apparent Oral Clearance (CL/F) | 0, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose |
Outcome results
None listed