A Phase I Pharmacokinetic Study of Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction

Status
Active
Cancer Type
Multiple Primaries
Trial Phase
Phase I
Eligibility
18 and over, Male and Female
Study Type
Treatment
NCD ID
NCT01273155
Protocol IDs
110060 (primary)
11-C-0060
Study Sponsor
National Cancer Institute

Summary

Background:

  • Belinostat is an experimental cancer treatment drug that works by helping to turn on genes that limit cell growth and survival of the tumor that are switched off in cancer cells. Belinostat has been given to patients with different types of cancer to measure its safety and effectiveness, but it has not been given in a formal trial to cancer patients who have abnormal liver function. Because belinostat is processed by the liver, its safety and effectiveness needs to be established in individuals who have abnormal liver function. Researchers are interested in comparing the effects of belinostat as a cancer treatment drug in individuals with normal and abnormal liver function.

Objectives:

  • To test the safety and effectiveness of belinostat in individuals who have solid tumors and lymphomas and who also have abnormal liver function.
  • To compare the results of belinostat treatment in individuals with normal and abnormal liver function.

Eligibility:

  • Individuals at least 18 years of age who have been diagnosed with solid tumors or lymphomas that have not responded to standard treatment.
  • Individuals with normal liver function and varying degrees of abnormal liver function (mild, moderate, severe) are eligible.

Design:

  • Participants will be screened with a full medical history and physical examination, as well as blood and urine tests, and tumor imaging studies. Participants will then be divided into study groups based on their liver function.
  • Participants will receive belinostat in cycles of treatment. Except for cycle 1, all cycles will last 21 days. Cycle 1 will last 28 days. For cycle 1 only, participants will receive a single dose of belinostat 1 week before the regular 21-day treatment cycle starts.
  • In each cycle, participants will receive belinostat once a day for 5 days, and will be asked to keep a medication diary to record any side effects.
  • Participants will have regular clinic visits with blood and urine samples and imaging studies to evaluate the cancer's response to treatment.
  • Participants may continue to take belinostat for as long as the cancer responds to the treatment....

Objectives

Background:

  • Belinostat is a histone deacetylase (HDAC) inhibitor. HDACs are frequently deregulated in cancer cells, leading to an increase in deacetylation and the silencing of genes that normally control cell cycle arrest and apoptosis.
  • Belinostat has growth inhibitory activity in several malignancies in vitro and in vivo, both as a single agent and in combination with chemotherapeutic agents. Several Phase I and II clinical trials have been conducted to date in patients with solid tumor and hematologic malignancies; belinostat has been generally well tolerated.
  • Belinostat is metabolized in the liver and therefore, the safety and dosing of belinostat needs to be established in patients with varying degrees of hepatic dysfunction.

Objectives:

  • Establish the safety and tolerability of belinostat given on days 1-5 of 21-day cycles to patients with varying degrees of liver dysfunction.
  • Define the maximum tolerated dose (MTD) and recommended dose of belinostat given on days 1-5 of 21-day cycles to patients with varying degrees of liver dysfunction.
  • Evaluate the pharmacokinetics (PK) of one dose of belinostat (400 mg/m(2)) in patients with varying degrees of liver dysfunction.
  • Obtain preliminary evidence of anti-tumor activity at tolerable doses of belinostat in patients with varying degrees of liver dysfunction.
  • Determine polymorphisms in the UGT1A1 28 allele and correlate these with the observed toxicities and the PK of belinostat in patients with varying degrees of liver dysfunction.
  • Measure direct versus indirect bilirubin levels and correlate these with observed toxicities, PK, and UGT1A1 polymorphisms.

Eligibility:

-Adults with histologically confirmed solid tumors or lymphomas whose disease has progressed after standard therapy or who have no acceptable standard treatment options. Patients with normal and varying degrees of hepatic dysfunction (mild, moderate, and severe) are eligible.

Study Design:

-Patients will be divided into 4 cohorts based on their level of liver dysfunction. Belinostat will be administered IV over 30 minutes. On day -7 (Cycle 1 only), all patients will receive a single dose of 400 mg/m(2) belinostat. On days 1-5 of each cycle, patients will receive belinostat at a dose dependent on the level of hepatic dysfunction (see below). The total length of Cycle 1 will be 28 days; all other cycles will be 21 days. No more than 12 patients with normal hepatic function will be accrued.

Treatment Sites in Georgia


Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

Study Coordinator:
Julia Maloney
404-778-1805

Doctors:

Wayne B. Harris MD
Suresh S. Ramalingam MD
Bassel F El-Rayes MD
Taofeek K. Owonikoko MD