Advanced/Metastatic Solid Tumors
Conditions
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.
Interventions
DRUGPHA-793887
Escalating doses of PHA-793887 administered weekly by IV infusion for 3 consecutive weeks in 4-week cycles.
Sponsors
Nerviano Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determination of Dose Limiting Toxicities and Maximum Tolerated Dose | First cycle |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of pharmacodynamics: biomarkers modulation in skin and tumor samples of consenting patients at baseline and post-treatment. | First cycle |
| 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 |
Countries
France, United Kingdom
Outcome results
None listed