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

Pharmacyclics

Status and phase

Completed

Phase 1

Conditions

Hematologic Neoplasms

Neoplasms

Treatments

Drug: CRA-24781

Study type

Interventional

Funder types

Industry

Identifiers

NCT00473577

PCYC 0401

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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