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

September 26, 2011 updated by: Pharmacyclics LLC.

Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of PCI-24781 Administered Orally in Patients With Advanced Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Greenbrae, California, United States, 94904
        • California Cancer Care
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institue
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose limiting toxicity assessment at the end of the first 28 day cycle.
Time Frame: at the end of the first 28 day cycle
at the end of the first 28 day cycle

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmacyclics LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

November 19, 2007

First Submitted That Met QC Criteria

November 19, 2007

First Posted (Estimate)

November 21, 2007

Study Record Updates

Last Update Posted (Estimate)

September 28, 2011

Last Update Submitted That Met QC Criteria

September 26, 2011

Last Verified

September 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-0402

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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