Study of the Tolerability, Safety, and Pharmacokinetics of CRA-024781 in Cancer Patients

Two Phase, Open-Label, Sequential, Ascending Dose Study of the Tolerability, Safety, and Pharmacokinetics of CRA-024781 in Cancer Patients

To determine the maximum tolerated dose (MTD) of CRA-024781 IV given by 2-hour intravenous infusions in patients with refractory solid or hematologic malignancies. To evaluate safety and tolerability, pharmacokinetics and pharmacodynamics, and to evaluate bioavailability of CRA-024781 IV when administered in a single oral dose.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Hematologic Neoplasms
• Intervention / Treatment: Drug: CRA-24781

Detailed Description

Patients will receive a single oral dose of CRA-024781 one week before beginning intravenous dosing. Blood samples for pharmacokinetic and pharmacodynamic analysis will be collected on several occasions prior to the start of the intravenous treatment.

The intravenous treatment will consist of 3 consecutive days of CRA-024781 IV administered as a 2-hour IV infusion every 3 weeks in a 4 weeks cycle.

Assessment of the extent of disease will be performed every 8 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60643
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥ 18 years
• histologically confirmed solid or hematologic malignancy that is refractory to standard therapy or for which no standard therapy exists
• estimated life expectancy > 12 weeks
• ECOG performance grade ≤ 2
• creatinine ≤ 1.5 X institutional upper limit of normal or creatinine clearance > 50 mL/min
• total bilirubin within institutional limits (unless elevated from documented Gilbert's syndrome)
• AST and ALT ≤ 2.5 X institutional upper limit of normal (≤ 5 x institutional upper limit of normal in the presence of liver metastases)
• platelet count ≥ 100,000/µL
• absolute neutrophil count (ANC) ≥ 1500/µL
• Hgb ≥ 9.0 g/dL
• patients with previously treated brain metastases who are not on corticosteroids are eligible
• effective contraceptive method (e.g., intrauterine device, oral contraceptive, or barrier device) must be used during the study by male and female patients of childbearing potential
• ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

• patients who have had immunotherapy, chemotherapy, or radiotherapy within 4 weeks (within 6 weeks for nitrosoureas or mitomycin C) prior to study entry; study entry defined as first day of drug dosing
• patients who have undergone major surgery within 4 weeks prior to study entry
• patients who are receiving another investigational drug
• patients with active CNS metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy
• uncontrolled illness including but not limited to: ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements
• risk factors for QTc prolongation and/or Torsade de Pointes
• patients with known HIV infection
• concurrent systemic hormonal therapy except: stable LHRH agonist therapy for prostate cancer; hormonal therapy (e.g., megestrol) for appetite stimulation; nasal, ophthalmic, and topical glucocorticoid preparations when appropriate; stable oral glucocorticoid and mineralocorticoid replacement for adrenal insufficiency; or oral contraceptives
• patients who have other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study agent
• pregnant or lactating women (female patients must have a negative serum pregnancy test within 7 days of study entry)
• patients who have previously received histone deacetylase inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Collaborators and Investigators

• Sponsor: Pharmacyclics LLC.

Publications and helpful links

Helpful Links

• Pharmacyclics

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (ACTUAL): November 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: May 11, 2007
• First Submitted That Met QC Criteria: May 14, 2007
• First Posted (ESTIMATE): May 15, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): August 25, 2010
• Last Update Submitted That Met QC Criteria: August 24, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: PCYC 0401