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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: PF-03084014

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-03084014	Drug: PF-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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): June 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: June 2, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Estimate): October 7, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: A8641021