Study of the Safety and Tolerability of Oral Capsule Form of PCI-24781 in Advanced Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00562224
Recruitment Status : Completed
First Posted : November 21, 2007
Last Update Posted : September 28, 2011
Information provided by (Responsible Party):
Pharmacyclics LLC.

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.

Condition or disease Intervention/treatment Phase
Neoplasms by Site Lymphoma, Non-hodgkin Hodgkin Disease Multiple Myeloma Leukemia, Lymphocytic, Chronic Drug: PCI-24781 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of PCI-24781 Administered Orally in Patients With Advanced Cancer
Study Start Date : November 2007
Actual Primary Completion Date : June 2010
Actual Study Completion Date : September 2010

Arm Intervention/treatment
Experimental: Arm 1
All study subjects will receive PCI-24781 (study drug).
Drug: PCI-24781
Up to 7 cohorts will receive PCI-24781 orally at doses starting at 30 mg/m2 three times a day approximately 4 hours apart ("TID"), up to 90 mg/m2, administered 5 days/week during the first 21 days of each 28 day cycle until MTD is reached. If a dose limiting toxicity (DLT) occurs, then the next cohort will receive PCI-24781 twice a day approximately 4 hours apart ("BID"). If a DLT occurs on the "BID" schedule, the subsequent cohort will receive PCI-24781 BID for 7 days every other week (2 times in a 28 day cycle). If a DLT occurs on this dosing schedule, then the next cohort will receive PCI-24781 BID for 5 days/week every other week (2 times in a 28 day cycle) until the maximum tolerated dose is reached.

Primary Outcome Measures :
  1. Dose limiting toxicity assessment at the end of the first 28 day cycle. [ Time Frame: at the end of the first 28 day cycle ]

Secondary Outcome Measures :
  1. Measure: Adverse event assessed through 30 days after last dose of study drug Measure: Tumor response Measure: Pharmacokinetic/Pharmacodynamic assessments [ Time Frame: 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00562224

United States, California
California Cancer Care
Greenbrae, California, United States, 94904
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Tennessee
Sarah Cannon Research Institue
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pharmacyclics LLC.
Principal Investigator: Samir Undevia, MD University of Chicago

Additional Information:
Responsible Party: Pharmacyclics LLC. Identifier: NCT00562224     History of Changes
Other Study ID Numbers: PCYC-0402
First Posted: November 21, 2007    Key Record Dates
Last Update Posted: September 28, 2011
Last Verified: September 2011

Keywords provided by Pharmacyclics LLC.:
Neoplasms by site
Lymphoma, non-hodgkin
Hodgkin disease
Multiple myeloma
Leukemia, lymphocytic, chronic

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Hodgkin Disease
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Neoplasms by Site
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Leukemia, B-Cell
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action