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

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

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.

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.