NeoplasmsPhase 1NCT01273155

Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction

A Phase 1 study testing Belinostat in people with Neoplasms and Lymphomas, run by National Cancer Institute (NCI) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 110 years
Conditions the study is for: Neoplasms, Lymphomas
What is being tested?: Belinostat
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 72 participants
Where: 7 sitesUnited States
Study dates: 10 Jan 2011to 25 Oct 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 110 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) solid tumor or lymphoma that is metastatic, unresectable, progressive, or recurrent, and for which standard curative or palliative measures do not exist or are no longer effective.
No radiation, major surgery, chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C); greater than or equal to 2 weeks since any prior administration of study drug in an exploratory Investigational New Drug (IND)/Phase 0 study. (also referred to as an "early Phase I study" or "pre-Phase I study" where a sub-therapeutic dose of drug is administered) at the Principal Investigator's (PI's) discretion. Patients must have recovered to at least eligibility levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy.
Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of belinostat in patients < 18 years of age, children are excluded from this study but will be eligible for future pediatric Phase I single-agent trials.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent.
Life expectancy of greater than 3 months.
Patients must have acceptable renal and marrow function as defined below:

Show all 15Show fewer

leukocytes greater than or equal to 3,000/mcL
absolute neutrophil count greater than or equal to 1,500/mcL
platelets greater than or equal to 100,000/mcL
serum creatinine within normal institutional limits OR creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above institutional normal, as determined by a measured 24-hour creatinine clearance Baseline evaluations should be conducted within 7 days of treatment start date.
Patients with abnormal liver function will be eligible. Patients with active hemolysis should be excluded. No distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes.
Patients with biliary obstruction for which a stent has been placed are eligible, provided the stent has been in place for at least 10 days prior to the first dose of belinostat and the liver function has stabilized. Two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function. There should be no evidence of biliary sepsis.
Patients with gliomas or brain metastases who require corticosteroids or anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to enrollment. Patients with known brain metastases should have had brain irradiation (whole brain or gamma knife) more than 4 weeks before starting the protocol. Note that patients should have had their steroids tapered to low dose (i.e., < 1.5 mg of dexamethasone/day).
The effects of belinostat on the developing human fetus are unknown. For this reason and because histone deacetylase (HDAC) inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

Prior therapy with belinostat.
Patients may not be receiving any other investigational agents.
Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to belinostat, including hydroxamate compounds or arginine.
Patients should not have taken valproic acid, another HDAC inhibitor, for at least 2 weeks prior to enrollment.
Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because belinostat is an HDAC inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with belinostat, breastfeeding should be discontinued if the mother is treated with belinostat.

Show all 9Show fewer

Human Immunodeficiency Virus (HIV) positive patients who are not on retroviral therapy will not be excluded from cohort 1, the normal liver function cohort. HIV positive patients who are not on retroviral therapy will be excluded from cohorts 2-4 because of confounding effects from potential complications from HIV and opportunistic infections.
HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for the increased risk of liver dysfunction from the antiretroviral therapies themselves and because of potential pharmacokinetics (PK) interactions with belinostat. Appropriate studies will be undertaken in these groups of patients when indicated.
Patients with significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), symptomatic congestive heart failure, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of frequency adjusting medication for atrial fibrillation is allowed, if stable medication for at least last month prior to initiation of belinostat treatment and medication not listed as causing Torsades de Points), or evidence of acute ischemia on electrocardiogram (ECG). Marked baseline prolongation of Q wave, T wave (QT)/Corrected QT Interval (QTc) interval, e.g., repeated demonstration of a QTc interval > 450 msec; Long QT Syndrome; the required use of concomitant medication that may cause Torsades de Pointes.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Emory University
Atlanta, Georgia, 30322-1102
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
University of California, Davis
Davis, California, 95616
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope National Medical Center
Duarte, California, 91010
USC Norris Cancer Center
Los Angeles, California, 90033
Albert Einstein College of Medicine
The Bronx, New York, 10461

Other trials in United States

About this study

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

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 cancer's response to treatment.
Participants may continue to take belinostat for as long as the cancer responds to the treatment.

Read the 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 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.
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 mg/m(2) 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.

Conditions: Neoplasms, Lymphomas
Being tested: Belinostat
Keywords: Histone Deacetylase Inhibitor, Liver Dysfunction, Pharmacokinetics, UGT1A1 Polymorphisms, Solid Tumor, Cancer, Lymphoma
Medical subject headings: Neoplasms, Lymphoma, Liver Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BelinostatDrug
Also called Beleodaq
Belinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).

Study groups in NCT01273155
Study group	Role	What they receive
Normal Function-Belinostat 1000 mg/m(2)	Active comparator	Normal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN. Receives: Drug: Belinostat
Mild Dysfunction-Belinostat 750 mg/m(2)	Experimental	Mild Liver Dysfunction was defined as bilirubin >Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) > ULN. Receives: Drug: Belinostat
Mild Dysfunction-Belinostat 1000 mg/m(2)	Experimental	Mild Liver Dysfunction was defined as bilirubin >Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) > ULN. Receives: Drug: Belinostat
Moderate Dysfunction-Belinostat 500 mg/m(2)	Experimental	Moderate Liver Dysfunction was defined as bilirubin >1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Receives: Drug: Belinostat
Moderate Dysfunction-Belinostat 750 mg/m(2)	Experimental	Moderate Liver Dysfunction was defined as bilirubin >1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST). Receives: Drug: Belinostat
Severe Dysfunction-Belinostat 250 mg/m(2)	Experimental	Severe Liver Dysfunction was defined as bilirubin >3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Receives: Drug: Belinostat
Severe Dysfunction-Belinostat 350 mg/m(2)	Experimental	Severe Liver Dysfunction was defined as bilirubin >3 but ≤ 10 x ULN and any aspartate aminotransferase (AST). Receives: Drug: Belinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose Limiting Toxicity (DLTs)
A DLT was defined as an adverse event deemed possibly, probably, or definitely related to administration of study drugs and met the following criteria: grade≥3 non-hematological toxicity (except grade ≥3 diarrhea, nausea, vomiting responsive to supportive therapy);grade≥3 rise in creatinine (except grade 3 able to be corrected to grade 1 or baseline with intravenous fluids within 24hrs); grade≥3 electrolyte toxicities (except those able to be corrected to grade 1 or baseline within 48hrs); grade 4 thrombocytopenia; grade 4 neutropenia for >5 days or febrile neutropenia; any neurotoxicity grade≥2 not reversible to grade 1 or baseline within 2wks; or any delay in treatment by ≥2wks due to treatment-related toxicity. Worsening liver function, as defined by a rise in serum bilirubin not related to tumor progression, was considered a DLT if a patient with mild dysfunction became severe for 1wk, or if a patient in either the moderate/severe groups had a >1.5x increase in bilirubin for 1 wk.
Measured: First cycle of therapy, 28 days.
Maximum Tolerated Dose (MTD) of Belinostat According to Degree of Liver Dysfunction
In order to maintain consistent dosing across the hepatic dysfunction groups, the dose recommended for cohorts with greater liver dysfunction could be no greater than the dose for cohorts of lesser dysfunction. In other words, it was assumed that a particular group would not tolerate a dose not tolerated by a group with lesser dysfunction and conversely, will tolerate a dose tolerated by a group with greater dysfunction. If a higher dose was tolerated in a group of greater dysfunction, but not in the group of lesser dysfunction, the lower dose would be recommended for both groups. The highest dose to be explored was no greater than the recommended dose for patients with normal liver function.
Measured: First cycle of therapy, 28 days
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug
The number of participants experiencing each adverse event by liver function cohort at each dose level. The grade refers to the severity of the Adverse Event. Grade 1 Mild; Grade 2 Moderate; Grade 3 Severe or medically significant but not immediately life-threatening; Grade 4 Life-threatening consequences; Grade 5 Death related to adverse event.
Measured: From Cycle 1 Day -7 up to 12 (21-day) cycles
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax)
Maximum plasma concentrations (Cmax) for belinostat and five metabolites on Cycle 1 Day -7 as a function of degree of liver dysfunction.
Measured: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf)
Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for belinostat and four metabolites on Cycle 1 Day -7 as a function of degree of liver dysfunction.
Measured: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after start of infusion; and 5, 10, 15, 60, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) of Belinostat
Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) for Belinostat glucuronide, a Belinostat Metabolite on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Measured: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2)
Half-life Period (t1/2) of belinostat and five metabolites on Cycle 1 Day -7 as a function of degree of liver function.
Measured: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Clearance (CL)
Clearance (CL) of Belinostat on Cycle 1 Day-7 as a function of degree of liver dysfunction
Measured: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Volume of Distribution at Steady State (Vss)
Belinostat Apparent volume of distribution at steady state (Vss) on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Measured: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway
Metabolic ratios of Maximum Plasma Concentrations (Cmax), reported as a geometric mean (geometric standard deviation), for the belinostat metabolic pathway on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Measured: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway
Metabolic ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf), reported as geometric mean (geometric standard deviation), for the belinostat metabolic pathway on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Measured: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.

Secondary outcomes (2)

Best Response
Radiologic response assessments by computed tomography (CT) scans were performed at baseline and every two cycles of treatment based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Per RECIST v1.1 Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD), neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for Progression of Disease (PD), taking as reference the smallest sum diameters while on study; PD, >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and an absolute increase of at least 5mm or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Measured: at baseline and every two 21-day cycles of treatment, up to 12 cycles
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Measured: From Cycle 1 Day -7 up to 12 (21-day) cycles.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jan 201125 Oct 2017

First posted10 Jan 2011 (estimated)
Study start10 Jan 2011
Primary completion25 Oct 2017
Study completion25 Oct 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01273155
Sponsor's protocol ID: 110060
Other IDs: 11-C-0060
Status last verified: Mar 2019
First submitted: 7 Jan 2011
Last updated: 26 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8.
PubMed 12939461
Gimsing P. Belinostat: a new broad acting antineoplastic histone deacetylase inhibitor. Expert Opin Investig Drugs. 2009 Apr;18(4):501-8. doi: 10.1517/13543780902852560.
PubMed 19335278
Marks PA, Richon VM, Rifkind RA. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst. 2000 Aug 2;92(15):1210-6. doi: 10.1093/jnci/92.15.1210.
PubMed 10922406

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer

All Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Pharmacokinetic Study of Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction
ClinicalTrials.gov ID: NCT01273155
Acronym / sponsor ID: 110060
Conditions: Neoplasms, Lymphomas
Keywords: Histone Deacetylase Inhibitor, Liver Dysfunction, Pharmacokinetics, UGT1A1 Polymorphisms, Solid Tumor, Cancer, Lymphoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 10 Jan 2011 (actual)
Primary completion: 25 Oct 2017 (actual)
Study completion: 25 Oct 2017 (actual)
First posted: 10 Jan 2011 (estimated)
Results: Posted 26 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 cancer's 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 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.
Measure direct versus indirect bilirubin levels and correlate these with observed toxicities, PK.

Eligibility:

Study Design:

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 7

Arm	Type	Receives
Normal Function-Belinostat 1000 mg/m(2)	Active comparator	Drug: BelinostatNormal Liver Function was defined as bilirubin ≤Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) ≤ ULN.
Mild Dysfunction-Belinostat 750 mg/m(2)	Experimental	Drug: BelinostatMild Liver Dysfunction was defined as bilirubin >Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) > ULN.
Mild Dysfunction-Belinostat 1000 mg/m(2)	Experimental	Drug: BelinostatMild Liver Dysfunction was defined as bilirubin >Upper Limit of Normal (ULN) but ≤1.5 x ULN and/or aspartate aminotransferase (AST) > ULN.
Moderate Dysfunction-Belinostat 500 mg/m(2)	Experimental	Drug: BelinostatModerate Liver Dysfunction was defined as bilirubin >1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST).
Moderate Dysfunction-Belinostat 750 mg/m(2)	Experimental	Drug: BelinostatModerate Liver Dysfunction was defined as bilirubin >1.5 to ≤ 3 x ULN and any aspartate aminotransferase (AST).
Severe Dysfunction-Belinostat 250 mg/m(2)	Experimental	Drug: BelinostatSevere Liver Dysfunction was defined as bilirubin >3 but ≤ 10 x ULN and any aspartate aminotransferase (AST).
Severe Dysfunction-Belinostat 350 mg/m(2)	Experimental	Drug: BelinostatSevere Liver Dysfunction was defined as bilirubin >3 but ≤ 10 x ULN and any aspartate aminotransferase (AST).

Who may qualify

Ages: 18 to 110 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) solid tumor or lymphoma that is metastatic, unresectable, progressive, or recurrent, and for which standard curative or palliative measures do not exist or are no longer effective.
No radiation, major surgery, chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C); greater than or equal to 2 weeks since any prior administration of study drug in an exploratory Investigational New Drug (IND)/Phase 0 study. (also referred to as an "early Phase I study" or "pre-Phase I study" where a sub-therapeutic dose of drug is administered) at the Principal Investigator's (PI's) discretion. Patients must have recovered to at least eligibility levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy.
Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of belinostat in patients < 18 years of age, children are excluded from this study but will be eligible for future pediatric Phase I single-agent trials.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent.
Life expectancy of greater than 3 months.

Key exclusion criteria (9 listed)

Prior therapy with belinostat.
Patients may not be receiving any other investigational agents.
Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to belinostat, including hydroxamate compounds or arginine.
Patients should not have taken valproic acid, another HDAC inhibitor, for at least 2 weeks prior to enrollment.
Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BelinostatAlso: BeleodaqBelinostat was administered intravenously (IV) over 30 minutes on days 1 through 5 of a 21-day cycle. All patients were administered a single dose of 400 mg/m(2) of belinostat on Cycle 1 Day -7 for pharmacokinetic analysis (the total length of Cycle 1 was 28 days).	Drug	Mild Dysfunction-Belinostat 1000 mg/m(2), Mild Dysfunction-Belinostat 750 mg/m(2), Moderate Dysfunction-Belinostat 500 mg/m(2), Moderate Dysfunction-Belinostat 750 mg/m(2), Normal Function-Belinostat 1000 mg/m(2), Severe Dysfunction-Belinostat 250 mg/m(2), Severe Dysfunction-Belinostat 350 mg/m(2)

Primary outcome

Dose Limiting Toxicity (DLTs)
Time frame: First cycle of therapy, 28 days.
A DLT was defined as an adverse event deemed possibly, probably, or definitely related to administration of study drugs and met the following criteria: grade≥3 non-hematological toxicity (except grade ≥3 diarrhea, nausea, vomiting responsive to supportive therapy);grade≥3 rise in creatinine (except grade 3 able to be corrected to grade 1 or baseline with intravenous fluids within 24hrs); grade≥3 electrolyte toxicities (except those able to be corrected to grade 1 or baseline within 48hrs); grade 4 thrombocytopenia; grade 4 neutropenia for >5 days or febrile neutropenia; any neurotoxicity grade≥2 not reversible to grade 1 or baseline within 2wks; or any delay in treatment by ≥2wks due to treatment-related toxicity. Worsening liver function, as defined by a rise in serum bilirubin not related to tumor progression, was considered a DLT if a patient with mild dysfunction became severe for 1wk, or if a patient in either the moderate/severe groups had a >1.5x increase in bilirubin for 1 wk.
Maximum Tolerated Dose (MTD) of Belinostat According to Degree of Liver Dysfunction
Time frame: First cycle of therapy, 28 days
In order to maintain consistent dosing across the hepatic dysfunction groups, the dose recommended for cohorts with greater liver dysfunction could be no greater than the dose for cohorts of lesser dysfunction. In other words, it was assumed that a particular group would not tolerate a dose not tolerated by a group with lesser dysfunction and conversely, will tolerate a dose tolerated by a group with greater dysfunction. If a higher dose was tolerated in a group of greater dysfunction, but not in the group of lesser dysfunction, the lower dose would be recommended for both groups. The highest dose to be explored was no greater than the recommended dose for patients with normal liver function.
Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug
Time frame: From Cycle 1 Day -7 up to 12 (21-day) cycles
The number of participants experiencing each adverse event by liver function cohort at each dose level. The grade refers to the severity of the Adverse Event. Grade 1 Mild; Grade 2 Moderate; Grade 3 Severe or medically significant but not immediately life-threatening; Grade 4 Life-threatening consequences; Grade 5 Death related to adverse event.
Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax)
Time frame: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Maximum plasma concentrations (Cmax) for belinostat and five metabolites on Cycle 1 Day -7 as a function of degree of liver dysfunction.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf)
Time frame: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after start of infusion; and 5, 10, 15, 60, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for belinostat and four metabolites on Cycle 1 Day -7 as a function of degree of liver dysfunction.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) of Belinostat
Time frame: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Area Under the Plasma Concentration Time Curve Extrapolated to Infinity(AUC0-inf) for Belinostat glucuronide, a Belinostat Metabolite on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2)
Time frame: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Half-life Period (t1/2) of belinostat and five metabolites on Cycle 1 Day -7 as a function of degree of liver function.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Clearance (CL)
Time frame: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Clearance (CL) of Belinostat on Cycle 1 Day-7 as a function of degree of liver dysfunction
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Volume of Distribution at Steady State (Vss)
Time frame: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Belinostat Apparent volume of distribution at steady state (Vss) on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Maximum Plasma Concentrations (Cmax) for the Belinostat Metabolic Pathway
Time frame: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Metabolic ratios of Maximum Plasma Concentrations (Cmax), reported as a geometric mean (geometric standard deviation), for the belinostat metabolic pathway on Cycle 1 Day-7 as a function of degree of liver dysfunction.
Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Metabolic Ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf) for the Belinostat Metabolic Pathway
Time frame: Cycle 1 Day-7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.
Metabolic ratios of Area Under the Plasma Concentration Time Curve Extrapolated to Infinity (AUC0-inf), reported as geometric mean (geometric standard deviation), for the belinostat metabolic pathway on Cycle 1 Day-7 as a function of degree of liver dysfunction.

2 secondary outcomes

Best Response
Time frame: at baseline and every two 21-day cycles of treatment, up to 12 cycles
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).
Time frame: From Cycle 1 Day -7 up to 12 (21-day) cycles.

Results and safety

Results posted to the registry on 26 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Function-Belinostat 1000 mg/m(2)	14	12
Mild Dysfunction-Belinostat 750 mg/m(2)	12	8
Mild Dysfunction-Belinostat 1000 mg/m(2)	18	6
Moderate Dysfunction-Belinostat 500 mg/m(2)	5	4
Moderate Dysfunction-Belinostat 750 mg/m(2)	5	3
Severe Dysfunction-Belinostat 250 mg/m(2)	10	5
Severe Dysfunction-Belinostat 350 mg/m(2)	8	2

Primary outcome: Dose Limiting Toxicity (DLTs)

Time frame: First cycle of therapy, 28 days.. Number. Unit: Toxicities

Measure	Normal Function-Belinostat 1000 mg/m(2) n = 12	Mild Dysfunction-Belinostat 750 mg/m(2) n = 8	Mild Dysfunction-Belinostat 1000 mg/m(2) n = 6	Moderate Dysfunction-Belinostat 500 mg/m(2) n = 4	Moderate Dysfunction-Belinostat 750 mg/m(2) n = 3	Severe Dysfunction-Belinostat 250 mg/m(2) n = 5	Severe Dysfunction-Belinostat 350 mg/m(2) n = 2
Value	0	0	0	0	0	0	0

Population analysed: Forty patients were evaluable for dose-limiting toxicity; others came off study prior to the end of Cycle 1 and were not evaluable.

Primary outcome: Maximum Tolerated Dose (MTD) of Belinostat According to Degree of Liver Dysfunction

Time frame: First cycle of therapy, 28 days. Number. Unit: mg/m(2)

Measure	Mild Dysfunction n = 14	Moderate Dysfunction n = 7	Severe Dysfunction n = 7
Value	1000	NA	NA

Population analysed: Normal liver function patients were not eligible for dose escalation. Twenty-eight patients were evaluable for MTD; others came off study prior to the end of Cycle 1 and were not evaluable.

Primary outcome: Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug

Time frame: From Cycle 1 Day -7 up to 12 (21-day) cycles. Count of participants. Unit: Participants

Measure	Normal Function-Belinostat 1000 mg/m(2) n = 14	Mild Dysfunction-Belinostat 750 mg/m(2) n = 10	Mild Dysfunction-Belinostat 1000 mg/m(2) n = 15	Moderate Dysfunction-Belinostat 500 mg/m(2) n = 5	Moderate Dysfunction-Belinostat 750 mg/m(2) n = 6	Severe Dysfunction-Belinostat 250 mg/m(2) n = 9	Severe Dysfunction-Belinostat 350 mg/m(2) n = 5
Grade 2 Anemia	1	1	3	0	1	0	1
Grade 3 Anemia	1	0	0	0	0	0	0
Grade 2 Anorexia	1	0	1	1	0	0	0
Grade 2 Dyspepsia	0	0	0	1	0	0	0
Grade 2 Dyspnea	1	0	0	1	0	0	0
Grade 2 Edema (limbs)	0	0	0	0	0	1	0
Grade 2 Fatigue	2	1	2	1	1	1	0
Grade 3 Fatigue	1	1	2	0	2	0	0

Population analysed: Total number of evaluable patients per cohort on the indicated dose level; only patients who received study drug were evaluable for assessment of toxicity (some patients were assigned to a dose level but did not receive study drug and are therefore not included).

Primary outcome: Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax)

Time frame: Cycle 1 Day -7 prior to infusion; 15 and 25 minutes after the start of infusion; and 5, 10, 15, 30, 60, and 90 minutes, and 2, 4, 6, 8, and 24 hours after the end of infusion.. Mean (Standard Deviation). Unit: µg/mL

Measure	Normal Function n = 14	Mild Dysfunction n = 25	Moderate Dysfunction n = 10	Severe Dysfunction n = 15
Belinostat	21.9 (8.7)	26.6 (9.5)	22.1 (5.7)	25.0 (7.4)
Belinostat glucuronide	80.8 (27.3)	90.8 (19.2)	67.2 (33.6)	72.8 (28.2)
Methyl belinostat	2.10 (0.94)	2.99 (1.15)	3.26 (0.75)	3.35 (0.90)
M21	1.26 (0.75)	1.79 (0.70)	1.64 (0.32)	1.93 (0.59)
M24	2.56 (0.77)	2.35 (0.96)	1.82 (0.65)	1.88 (0.96)
M26	1.68 (0.71)	1.80 (0.64)	1.83 (0.52)	2.24 (1.65)

Normal Function vs Mild Dysfunction vs Moderate Dysfunction vs Severe Dysfunction: Kendall's Tau: 0.096, p = 0.327, Jonckheere-Terpstra
Normal Function vs Mild Dysfunction vs Moderate Dysfunction vs Severe Dysfunction: Kendall's Tau: -0.178, p = 0.063, Jonckheere-Terpstra
Normal Function vs Mild Dysfunction vs Moderate Dysfunction vs Severe Dysfunction: Kendall's Tau: 0.382, p <0.001, Jonckheere-Terpstra

Population analysed: The number of patients in a given cohort that received Belinistat on Cycle 1 Day-7 and had blood samples successfully collected at the specified timepoints for PK analysis. There were 3 patients with Mild Liver Dysfunction who were not evaluable for Belinostat Cmax.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Cycle 1 Day -7 up to 12 (21-day) cycles.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Function-Belinostat 1000 mg/m(2)	5 of 14 (35.7%)	14 of 14 (100%)	0 of 14
Mild Dysfunction-Belinostat 750 mg/m(2)	6 of 12 (50%)	11 of 12 (91.7%)	1 of 12
Mild Dysfunction-Belinostat 1000 mg/m(2)	7 of 18 (38.9%)	14 of 18 (77.8%)	3 of 18
Moderate Dysfunction-Belinostat 500 mg/m(2)	4 of 5 (80%)	5 of 5 (100%)	1 of 5
Moderate Dysfunction-Belinostat 750 mg/m(2)	3 of 5 (60%)	4 of 5 (80%)	1 of 5
Severe Dysfunction-Belinostat 250 mg/m(2)	7 of 10 (70%)	9 of 10 (90%)	6 of 10
Severe Dysfunction-Belinostat 350 mg/m(2)	4 of 8 (50%)	6 of 8 (75%)	4 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12939461Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8.
Background: PubMed 19335278Gimsing P. Belinostat: a new broad acting antineoplastic histone deacetylase inhibitor. Expert Opin Investig Drugs. 2009 Apr;18(4):501-8. doi: 10.1517/13543780902852560.
Background: PubMed 10922406Marks PA, Richon VM, Rifkind RA. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst. 2000 Aug 2;92(15):1210-6. doi: 10.1093/jnci/92.15.1210.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Neoplasms

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Naoko Takebe, M.D., Ph.D. principal investigator

National Cancer Institute (NCI)

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Belinostat in people with Neoplasms and Lymphomas, run by National Cancer Institute (NCI) at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLTs) (time frame: First cycle of therapy, 28 days.). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01273155, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2019.