Phase 1
N=72
Belinostat for Solid Tumors and Lymphomas in Patients With Varying Degrees of Hepatic Dysfunction
Neoplasms · Lymphomas
Bottom Line
View on ClinicalTrials.gov: NCT01273155 ↗Enrolled (actual)
72
Serious AEs
50.0%
Results posted
Mar 2019
Primary outcome: Primary: Dose Limiting Toxicity (DLTs) — 0; 0; 0; 0 Toxicities
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Belinostat (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Oct 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Limiting Toxicity (DLTs) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Belinostat According to Degree of Liver Dysfunction |
1000; NA; NA | — |
| PRIMARY Number of Participants Experiencing Adverse Events Considered to be at Least Possibly Related to the Study Drug |
1; 1; 3; 0; 1; 0 | — |
| PRIMARY Pharmacokinetics (PK) of a Single-dose Belinostat (400 mg/m^2)) According to Degree of Liver Dysfunction: Maximum Plasma Concentrations (Cmax) |
21.9; 26.6; 22.1; 25.0; 80.8; 90.8 | 0.327 |
| PRIMARY 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) |
719; 859; 834; 1012; 354; 483 | 0.025 sig |
| PRIMARY 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 |
15.1; 18.4; 18.4; 23.4 | 0.548 |
| PRIMARY Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Half-Life (t1/2) |
118; 127; 144; 157; 280; 246 | 0.340 |
| PRIMARY Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Clearance (CL) |
661; 542; 505; 444 | 0.023 sig |
| PRIMARY Pharmacokinetics (PK) of Single-dose Belinostat (400 mg/m^2) According to Degree of Liver Dysfunction: Volume of Distribution at Steady State (Vss) |
30.1; 25.7; 38.1; 29.6 | 0.531 |
| PRIMARY 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 |
3.78; 3.57; 2.88; 2.85; 0.0948; 0.112 | 0.023 sig |
| PRIMARY 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 |
18.7; 21.8; 18.1; 17.7; 0.422; 0.574 | 0.568 |
| SECONDARY Best Response |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). |
14; 11; 14; 5; 4; 9 | — |
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 cancer's response to treatment.
* Participants may continue to take belinostat for as long as the cancer responds to the treatment.
Eligibility Criteria
INCLUSION CRITERIA
- 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 450 msec; Long QT Syndrome; the required use of concomitant medication that may cause Torsades de Pointes.
Data sourced from ClinicalTrials.gov (NCT01273155). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.