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NCT04175912

Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver

Active, enrolled Phase 2 Results posted Last updated 17 November 2025
What this trial tests

Phase 2 trial testing Carboplatin in Metastatic Cholangiocarcinoma in 40 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
16 March 2020
Primary endpoint
27 November 2023
31 October 2026

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment40
Start date16 March 2020
Primary completion27 November 2023
Estimated completion31 October 2026
Sites421 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Metastatic Cholangiocarcinoma or Metastatic Hepatocellular Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Primary · Every 3 months for the first year and every 6 months for years 2-3

Response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Objective response includes complete response (CR) and partial response (PR). CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

GroupValue95% CI
Arm A (Pevonedistat)0
Arm B (Pevonedistat, Paclitaxel, Carboplatin)0
Arm A (Pevonedistat)17
Arm B (Pevonedistat, Paclitaxel, Carboplatin)17
Clinical Benefit Secondary · Every 3 months for the first year and every 6 months for years 2-3

Clinical benefit was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1), including complete response (CR), partial response (PR) and stable disease (SD) that lasted greater than or equal to 24 weeks. CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither suffi

GroupValue95% CI
Arm A (Pevonedistat)0
Arm B (Pevonedistat, Paclitaxel, Carboplatin)1
Arm A (Pevonedistat)17
Arm B (Pevonedistat, Paclitaxel, Carboplatin)16
Progression-free Survival (PFS) Secondary · Every 3 months for the first year and every 6 months for years 2-3

PFS was defined as the time from randomization to progression or death, whichever came first; patients alive without evidence of disease progression were censored at the date of last disease assessment. Patients who died without documented progression and the death occurred \> 6 weeks of last disease assessment will be censored at the date of last disease assessment that showed progression-free. Progression was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1), defined as at least a 20% increase in the sum of the diameters of target lesi

GroupValue95% CI
Arm A (Pevonedistat)1.541.41 – 2.10
Arm B (Pevonedistat, Paclitaxel, Carboplatin)2.921.71 – 5.55
Overall Survival (OS) Secondary · Every 3 months for the first year and every 6 months for years 2-3

OS was defined as the time from randomization to death from any cause, and patients still living were censored at the date last known alive.

GroupValue95% CI
Arm A (Pevonedistat)4.804.04 – 12.50
Arm B (Pevonedistat, Paclitaxel, Carboplatin)6.544.20 – 14.80

Adverse events — posted to ClinicalTrials.gov

Time frame: Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A (Pevonedistat)
Serious: 8/17 (47%)
Deaths: 17/17
Arm B (Pevonedistat, Paclitaxel, Carboplatin)
Serious: 12/17 (71%)
Deaths: 15/17

Serious adverse events (41 terms)

ReactionSystemArm A (Pevonedistat)Arm B (Pevonedistat, Pacli…
Febrile neutropeniaBlood and lymphatic system disorders
FeverGeneral disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
CholecystitisHepatobiliary disorders
SepsisInfections and infestations
Acute kidney injuryRenal and urinary disorders
HypertensionVascular disorders
AnemiaBlood and lymphatic system disorders
Death NOSGeneral disorders
FatigueGeneral disorders
Disease progressionGeneral disorders
Abdominal distensionGastrointestinal disorders
AscitesGastrointestinal disorders
Colonic perforationGastrointestinal disorders
ConstipationGastrointestinal disorders
GastroparesisGastrointestinal disorders
IleusGastrointestinal disorders
VomitingGastrointestinal disorders
Hepatobiliary disorders - Other, specifyHepatobiliary disorders
Biliary tract infectionInfections and infestations
Hepatic infectionInfections and infestations
Infections and infestations - Other, specifyInfections and infestations
INR increasedInvestigations
Neutrophil count decreasedInvestigations
Other adverse events (135 terms — click to expand)

ReactionSystemArm A (Pevonedistat)Arm B (Pevonedistat, Pacli…
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Peripheral sensory neuropathyNervous system disorders
AnemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
ConstipationGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
DiarrheaGastrointestinal disorders
Blood lactate dehydrogenase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
Lymphocyte count decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
GGT increasedInvestigations
Neutrophil count decreasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
Edema limbsGeneral disorders
VomitingGastrointestinal disorders
Blood bilirubin increasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
Creatinine increasedInvestigations
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Sinus tachycardiaCardiac disorders
FeverGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
PainGeneral disorders
AscitesGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Mucositis oralGastrointestinal disorders
Weight lossInvestigations

Most-reported serious reactions: Febrile neutropenia, Fever, Abdominal pain, Nausea, Cholecystitis, Sepsis, Acute kidney injury, Hypertension.

Data from ClinicalTrials.gov NCT04175912 adverse events section.

Sponsor's own description

This phase II trial studies how well pevonedistat alone or in combination with chemotherapy (paclitaxel and carboplatin) works in treating patients with bile duct cancer of the liver. Pevonedistat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study may help the study doctors find out how well pevonedistat shrinks bile duct cancer of the liver when given alone and when in combination with paclitaxel and carboplatin.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  2. Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.
    Fu DJ, Wang T. · · 2023 · cited 45× · PMID 37525282 · DOI 10.1186/s13045-023-01485-7
  3. Transcription Factors: The Fulcrum Between Cell Development and Carcinogenesis.
    Islam Z, Ali AM, Naik A, Eldaw M, et al · · 2021 · cited 38× · PMID 34195082 · DOI 10.3389/fonc.2021.681377
  4. Targeting cullin neddylation for cancer and fibrotic diseases.
    He ZX, Yang WG, Zengyangzong D, Gao G, et al · · 2023 · cited 33× · PMID 37771770 · DOI 10.7150/thno.78876
  5. Recent Progress in the Systemic Treatment of Advanced/Metastatic Cholangiocarcinoma.
    Fostea RM, Fontana E, Torga G, Arkenau HT. · · 2020 · cited 29× · PMID 32932925 · DOI 10.3390/cancers12092599
  6. Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.
    Liu D, Che X, Wu G. · · 2024 · cited 25× · PMID 38191508 · DOI 10.1186/s40364-023-00545-x
  7. Systemic treatment options for advanced biliary tract carcinoma.
    Xie C, McGrath NA, Monge Bonilla C, Fu J. · · 2020 · cited 17× · PMID 32748173 · DOI 10.1007/s00535-020-01712-9
  8. The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.
    Tang H, Pang X, Li S, Tang L. · · 2024 · cited 11× · PMID 39062453 · DOI 10.3390/biom14070738

Verify or expand the search:

Other trials of Carboplatin

Trials testing the same drug.

Other recruiting trials for Metastatic Cholangiocarcinoma

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04175912.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing