Clinical trial NCT00562224: Study of the Safety and Tolerability of Oral Capsule Form of PCI-24781 in Advanced Cancer Patients
Official title: Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of PCI-24781 Administered Orally in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms by Site
Lymphoma, Non-hodgkin
Hodgkin Disease
Multiple Myeloma
Leukemia, Lymphocytic, Chronic
Keywords: PCI-24781
Neoplasms by site
Lymphoma, non-hodgkin
Hodgkin disease
Multiple myeloma
Leukemia, lymphocytic, chronic
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2007-11-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine the highest dose of study drug that can be taken without causing serious side effects in patients with advanced cancer. The study will look at safety of the study drug and whether the treatment schedule is tolerated by patients.


Eligibility criteria: Inclusion Criteria:

* age ≥ 18 years
* Histologically confirmed, measurable solid tumor, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, or multiple myeloma that has relapsed after standard therapy or for which no standard therapy exists
* Ability to swallow oral capsules without difficulty
* Estimated life expectancy \> 12 weeks
* ECOG performance status ≤ 2
* Creatinine ≤ 1.5 × institutional upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 × institutional ULN (unless elevated from documented Gilbert's syndrome)
* AST and ALT ≤ 2.5 × institutional ULN (≤ 5 × institutional ULN in the presence of liver metastases)
* Platelet count ≥ 100,000/µL
* ANC ≥ 1500/µL
* Hgb ≥ 9.0 g/dL
* Patients with previously treated, stable, asymptomatic brain metastases who are not on corticosteroids are eligible
* Willing and able 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 first day of drug dosing
* Patients who have undergone major surgery within 4 weeks prior to first day of drug dosing
* Patients who have received another investigational drug within 4 weeks
* Evidence of leptomeningeal metastasis
* Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of the oral drugs (eg, WDHA syndrome, carcinoid syndromes, diarrhea due to infections, malabsorption syndromes secondary to surgery or chemotherapy)
* 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
* Patients with risk factors for, or who are receiving medications known to prolong QTc interval and that may be associated with Torsades de Pointes
* QTc prolongation (defined as a QTc interval ≥ 450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
* History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
* Patients with known HIV infection
* Pregnant or lactating women (female patients of child-bearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or, if positive, a pregnancy ruled out by ultrasound)

Primary outcomes:
measure: Dose limiting toxicity assessment at the end of the first 28 day cycle.
timeFrame: at the end of the first 28 day cycle
Secondary outcomes:
measure: Measure: Adverse event assessed through 30 days after last dose of study drug Measure: Tumor response Measure: Pharmacokinetic/Pharmacodynamic assessments
timeFrame: AE through 30 days after last dose of study drug, Tumor response at the end of every 2nd 28 day cycle, PK/PD assessments on Day 1, 2, 3 (or 4 or 5), and Day 8 of cycle 1
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: California Cancer Care
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Nashville
country: United States
facility: Sarah Cannon Research Institue
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: University of Chicago
name: Samir Undevia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17. doi: 10.1158/1535-7163.MCT-05-0442.