Dose-Escalation Study of PHA-793887 in Patients With Advanced/Metastatic Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The purpose of this open-label, multi center, phase I study, was to determine the safety profile of PHA-793887 administered by intravenous infusion to patients with advanced/metastatic solid tumors. This was a dose-finding study to determine the maximum tolerated dose and the dose of PHA-793887 that can be safely used in phase II investigations.

Official Title
-----------------
A Phase I Dose-Escalation Study of PHA-793887 Administered as a 1-hour IV Infusion on Days 1, 8 and 15 in a 4-Week Cycle in Patients With Advanced/Metastatic Solid Tumors

Conditions
-----------------
Advanced/Metastatic Solid Tumors

Intervention / Treatment
-----------------
* Drug: PHA-793887


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced/metastatic solid tumors for which no standard therapy exists ECOG (WHO) performance status 0-1 Life expectancy of at least 3 months Age ≥ 18 years Adequate liver, pancreas and renal function Acceptable hematologic status Acute toxic effects from prior therapy must be resolved to NCI CTCAE Grade ≤ 1 Treatment with surgery, chemotherapy, or investigational therapy must be completed at least one month prior to treatment initiation (6 weeks for nitrosoureas or Mitomycin C and liposomal doxorubicin) Prior radiation therapy allowed in no more than 25% of bone marrow reserve Men and women of child-producing potential must agree upon the use of effective contraceptive methods Exclusion Criteria: In the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis Known brain metastases Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1 Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy Pregnant or breast feeding women Known infection with HIV, active hepatitis B or hepatitis C Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation History of pancreatitis or disorders making the patient at risk of pancreatitis Previous history or current presence of neurological disorders Patients with pre-existing symptoms of peripheral neuropathy not related to prior anticancer therapy(ies) Concomitant treatment that may be associated with peripheral neuropathy Other severe concurrent conditions that could compromise protocol objectives.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-Escalation<br> | Drug: PHA-793887<br>* Escalating doses of PHA-793887 administered weekly by IV infusion for 3 consecutive weeks in 4-week cycles.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Dose Limiting Toxicities and Maximum Tolerated Dose |  | First cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Adverse Events (based on CTCAE version 3.0) |  | All cycles | 
| Evaluation of pharmacokinetics: plasma concentrations at different times after dosing and related assessment of conventional pharmacokinetic parameters. |  | First 2 cycles | 
| Evaluation of pharmacodynamics: biomarkers modulation in skin and tumor samples of consenting patients at baseline and post-treatment. |  | First cycle |