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.

Study Overview

• Status: Terminated
• Conditions: Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Drug: PHA-793887

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuif Cedex, France, 94805
    • Institut Gustave-Roussy
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St. James University Hospital

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Nerviano Medical Sciences
• Investigators: Principal Investigator: Jean-Charles Soria, MD Professor, Institut Gustave-Roussy, Villejuif Cedex, France; Principal Investigator: Chris Twelves, MD Professor, St James University Hospital, Leeds, UK

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: October 14, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimate): October 16, 2009

Study Record Updates

• Last Update Posted (Estimate): October 16, 2009
• Last Update Submitted That Met QC Criteria: October 15, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CDKC-887-001; EudraCT Number: 2006-002149-35