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Belinostat, Warfarin

Phase 2

Peripheral T-cell Lymphoma | Small molecule | Oncology |Assertio Holdings, Inc.|Last Updated: Oct 29, 2021

Target and mechanism

Molecular targetHDAC1, HDAC3, HDAC6, HDAC2, HDAC5, HDAC7
Target classInhibitor
ModalitySmall molecule

Also known as oral belinostat, belinostat, belinostat, carboplatin, paclitaxel, Belinostat

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment129

FDA Designations

No designations recorded

Clinical trial landscape

Belinostat, Warfarin · 4 trials · 5 indications

Phase 2 2Phase 1 2
NCT00873119Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown PrimaryCarcinoma of Unknown Primary
COMPLETED89 Analytics
NCT00865969Belinostat in Relapsed or Refractory Peripheral T-Cell LymphomaPeripheral T-cell Lymphoma
COMPLETED129 Analytics
PHASE2COMPLETED
Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary
Carcinoma of Unknown PrimaryUnlock trial analytics
PHASE2COMPLETED
Belinostat in Relapsed or Refractory Peripheral T-Cell Lymphoma
Peripheral T-cell LymphomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression Free Survival
Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Time from the date of randomization to the time of disease progression or death due to any cause, measured by RECIST criteria (Response Evaluation Criteria In Solid Tumors).

Objective Response Rate
24 months

Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to International Working Group (IWG) criteria. The response was assessed based on clinical and radiological criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites. As pre-defined, the primary endpoint analysis for this study was based on the Independent Review Committee (IRC) assessment of response.

Safety, tolerability and maximum tolerated dose of orally administered PXD101 for each cohort
throughout the study
Plasma concentration and pharmacodynamic effects of warfarin
34 days

Samples will be analyzed for S-warfarin and R-warfarin analytes in all evaluable subjects at the end of the trial

Pharmacokinetic evaluation of belinostat
34 days

Pharmacokinetic evaluation of belinostat 1,000 mg/m2 and metabolites in the presence of warfarin 5mg

Secondary Endpoints

Best Overall Response
Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study
Overall Survival (OS)
Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study
Time to Response
Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm A - BelCaPEXPERIMENTALGroup A: belinostat 1000 mg/m² administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat 2000 mg administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel 175 mg/m² administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.
Arm B - CaPACTIVE_COMPARATORGroup B: paclitaxel 175 mg/m² administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
BelinostatEXPERIMENTALBelinostat 1000 mg/m\^2 administered as a 30 minute IV infusion on Days 1-5 of every 3-week cycle until disease progression or unmanageable treatment-related toxicities.
oral belinostatEXPERIMENTAL -
Warfarin, BelinostatEXPERIMENTALWarfarin 5 mg po will be given on Day -14 and Day 3. Belinostat 1000 mg/m² will be given as a 30 minute IV infusion on Days 1 - 5

Interventions

NameTypeDescription
belinostat, carboplatin, paclitaxelDRUG -
carboplatin, paclitaxelDRUG -
BelinostatDRUG -
oral belinostatDRUGoral belinostat dosed once or twice daily at continuous and discontinuous dosing schedules.
Belinostat, WarfarinDRUG1000 mg/m2 injection infusion given in a 30 min period plus Warfarin 5mg PO
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites23

Inclusion Criteria: * Patients with CUP where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography (CT) scan of the chest, abdomen and pelvis, bilateral mammography (in women with adenocarcinoma ...

Countries:United StatesDenmarkFranceGermanyBelgiumCanadaCroatiaHungaryIsraelItalyNetherlandsPolandRussiaSlovakiaSouth AfricaSpainUnited Kingdom
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Frequently asked questions about Belinostat, Warfarin

What is belinostat used for?

Belinostat is an investigational small molecule studied in oncology for peripheral T-cell lymphoma, carcinoma of unknown primary, and solid tumors. It has been evaluated both as a single agent and in combination regimens, including with carboplatin and paclitaxel, and separately in a study with warfarin in patients with solid tumors or hematological malignancies.

What does belinostat target?

Belinostat targets histone deacetylases, specifically HDAC1, HDAC2, HDAC3, HDAC5, HDAC6, and HDAC7. It acts as an HDAC inhibitor, a class of small molecule agents that modulate histone acetylation. This target profile underlies its development as an anticancer therapy across lymphoma and solid tumor indications.

Who is developing belinostat?

Belinostat is being developed by Assertio Holdings, Inc., which trades under the ticker ASRT. The company is the sponsor associated with the clinical development program for this HDAC inhibitor across its oncology indications.

What phase is belinostat in?

Belinostat is in Phase 2 clinical development. It is investigational and has been studied in completed Phase 1 and Phase 2 trials. The Phase 2 program includes evaluation in carcinoma of unknown primary and in relapsed or refractory peripheral T-cell lymphoma, while Phase 1 studies covered solid tumors, lymphoma, and hematological malignancies.

What clinical trials is belinostat in?

Belinostat has been studied in completed trials including NCT00873119, a Phase 2 study of belinostat with carboplatin and paclitaxel in carcinoma of unknown primary, and NCT00865969, a Phase 2 study in relapsed or refractory peripheral T-cell lymphoma. Earlier Phase 1 trials include NCT01317927 with warfarin and NCT00413075 of oral PXD101 in advanced solid tumors or lymphoma.

Is belinostat the same as oral belinostat or PXD101?

Yes. Belinostat is also known as oral belinostat and PXD101. These names refer to the same HDAC inhibitor, and the oral formulation was studied under the PXD101 designation in a Phase 1 trial in patients with advanced solid tumors or lymphoma.