Ignite Creation Date:
2024-05-05 @ 11:11 PM
Last Modification Date:
2024-10-26 @ 10:30 AM
Study NCT ID:
NCT01273155
Status:
COMPLETED
Last Update Posted:
2019-03-26
First Post:
2011-01-07
Brief Title:
Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Pharmacokinetic Study of Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction
Status:
COMPLETED
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
- Belinostat is an experimental cancer treatment drug that works by helping to turn on genes that limit cell growth and survival of cancer cells These genes are often switched off in tumors 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 sample collection and imaging studies to evaluate the cancers response to treatment
Participants may continue to take belinostat for as long as the cancer responds to the treatment
- Belinostat is an experimental cancer treatment drug that works by helping to turn on genes that limit cell growth and survival of cancer cells These genes are often switched off in tumors 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 sample collection and imaging studies to evaluate the cancers response to treatment
Participants may continue to take belinostat for as long as the cancer responds to the treatment
Detailed Description:
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 through 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 through 5 of 21-day cycles to patients with varying degrees of liver dysfunction
Evaluate the pharmacokinetics PK of one dose of belinostat 400 mgm2 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
Measure direct versus indirect bilirubin levels and correlate these with observed toxicities PK
Eligibility
-Adults with 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 dose escalation cohorts based on their level of liver dysfunction Belinostat will be administered intravenously IV over 30 minutes On day -7 Cycle 1 only all patients will receive a single dose of 400 mgm2 belinostat On days 1 through 5 of each cycle patients will receive belinostat at a dose dependent on the level of hepatic dysfunction and dose level Mild moderate and severe liver dysfunction cohorts will begin on dose level 1 patients with normal hepatic function will not have their dose escalated see below The total length of Cycle 1 will be 28 days all other cycles will be 21 days No more than 12 evaluable patients with normal hepatic function will be accrued
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 through 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 through 5 of 21-day cycles to patients with varying degrees of liver dysfunction
Evaluate the pharmacokinetics PK of one dose of belinostat 400 mgm2 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
Measure direct versus indirect bilirubin levels and correlate these with observed toxicities PK
Eligibility
-Adults with 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 dose escalation cohorts based on their level of liver dysfunction Belinostat will be administered intravenously IV over 30 minutes On day -7 Cycle 1 only all patients will receive a single dose of 400 mgm2 belinostat On days 1 through 5 of each cycle patients will receive belinostat at a dose dependent on the level of hepatic dysfunction and dose level Mild moderate and severe liver dysfunction cohorts will begin on dose level 1 patients with normal hepatic function will not have their dose escalated see below The total length of Cycle 1 will be 28 days all other cycles will be 21 days No more than 12 evaluable patients with normal hepatic function will be accrued
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 11-C-0060 | None | None | None |