Clinical trial NCT00996255: Dose-Escalation Study of PHA-793887 in Patients With Advanced/Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumors
Lead sponsor: Nerviano Medical Sciences
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Determination of Dose Limiting Toxicities and Maximum Tolerated Dose
timeFrame: First cycle
Secondary outcomes:
measure: Assessment of Adverse Events (based on CTCAE version 3.0)
timeFrame: All cycles
measure: Evaluation of pharmacokinetics: plasma concentrations at different times after dosing and related assessment of conventional pharmacokinetic parameters.
timeFrame: First 2 cycles
measure: Evaluation of pharmacodynamics: biomarkers modulation in skin and tumor samples of consenting patients at baseline and post-treatment.
timeFrame: First cycle
Other outcomes:
Locations:
city: Villejuif Cedex
country: France
facility: Institut Gustave-Roussy
city: Leeds
country: United Kingdom
facility: St. James University Hospital
Study officials:
affiliation: Institut Gustave-Roussy, Villejuif Cedex, France
name: Jean-Charles Soria, MD Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: St James University Hospital, Leeds, UK
name: Chris Twelves, MD Professor
role: PRINCIPAL_INVESTIGATOR
References: