Table 2

Inhibitors of epigenetic regulators validated in clinical trials in pancreatic cancer (terminated, completed trials and active, but not recruiting clinical trails)

CompoundEpigenetic targetCombinationTreatmentNCT numberOutcome measuresResults in PDACEnrolled tumour entitiesNo. of enrolled patients
Phase I and combined phase I/II
 VorinostatHDAC class I/IIMarizomibPalliative00667082MTD, pharmacokinetics, pharmacodynamics, toxicity and antitumour activity of the combination therapyNo antitumour activityPDAC, NSCLC
Multiple myeloma
 VorinostatHDAC class I/IIRadiation capecitabinePalliative+adjuvant00983268MTD, tumour response, toxicityNo results yetPeriampullary adenocarcinoma
 VorinostatHDAC class I/IIRadiation
Palliative00948688MTD, progression-free survival 7 months after registrationNo results yetPDAC50*
 VorinostatHDAC class I/IIRadiationPalliative00831493MTD, MOS, correlation of serum cytokine levels with symptoms and outcomeNo results yetPDAC3
 ValproateHDAC class IEpirubicin
Palliative00246103Safety, tolerability, MTD, pharmacokinetic profile, VPA effect on histone acetylation in blood cells and tumour biopsiesLow potency, but preferable toxicity profile, might be beneficial for patients with HDAC2 overexpressionAdvanced neoplasms44
 EntinostatHDAC class I13-cis retinoic acidPalliative00098891MTD, dose-limiting toxicity, pharmacokinetics, tumour responseStable disease in one patient with chemotherapy-resistant PDACMetastatic or advanced solid tumours or lymphomas24
 EntinostatHDAC class IPalliative00020579MTD and dose-limiting toxicity, pharmacokinetics, acetylation in blood cells, tumour responseNo results yetNot specified cancer75*
 MocetinostatHDAC classes I+IVGemcitabinePalliative00372437Phase I: MTD, response rate, determination of recommended phase II dose
Phase II: Overall response rate in combination with gemcitabine in gemcitabine-naïve patients in stage III and IV PDAC
Partial response and stabilised diseaseSolid tumours where gemcitabine is considered as standards of care, phase II limited to PDAC47
 CHR-3996HDAC class IPalliative00697879Safety, tolerability, dose-limiting toxicity, MTD, pharmacokinetics, antitumour activityReduction of liver metastases in one patient with acinar pancreatic cancerSolid tumours40
 RomidepsinHDAC class IGemcitabinePalliative00379639Dose-limiting toxicity, number of patients with adverse events, best overall response4/9 patients showed stable disease; additive haematological side effectsSolid tumours36
 OTX015Pan-BETPalliative02259114Number of dose-limiting toxicities at cycle 1No results yetNUT midline carcinoma
Breast cancer
NSCLC, castrate-resistant prostate cancer, PDAC
 Bay1238097Pan-BETPalliative02369029Incidence of dose-limiting toxicity, tumour responseNo results yetNeoplasms8
 BI-2536BRD4GemcitabinePalliative02215044Occurrence of dose-limiting toxicity, survival, tumour response, CA19-9 levels, maximal concentration of the analytes in plasmaNo results yetPancreatic neoplasms12
Phase II non-radomised
 PanobinostatHDAC class I/IIBortezomibPalliative01056601PFS, number of participants with tumour response, duration of response, characterisation of quality and quantity toxicityNo treatment response and severe treatment-related toxicity, study was closed ahead of schedulePDAC7
 Curcuminp300, CBPGemcitabinePalliative00192842Time to tumour progression, response rate, survival, clinical benefit, toxicityIn chemotherapy-naïve patients with advanced PDAC. Increased GI toxicityPDAC17
 Curcuminp300, CBPPalliative000944456 months survival, response rate, assessment of biological activity in blood mononuclear cells via signalling and apoptotic pathways, pharmacokineticsNo severe toxicity, curcumin showed biological activity with stable disease (1/22) and brief response (1/22) with 73% reduction of liver metastasis sizePDAC50
 BI-2536BRD4Palliative00710710Objective response, PFS, dose-limiting toxicity, overall survival, clinical benefit responseFirst-line therapy in patients with unresectable tumours, stable disease in 24.4% of patients; the second stage of the study which was supposed to test BI-2536 as a second-line therapy was not initiatedPancreatic neoplasms89
Phase II randomised
 CI-994HDAC class IGemcitabinePalliative00004861Efficiency and safety of CI-994 in combination with gemcitabineInferior compared with gemcitabine monotherapy with decreased quality of lifePDAC
  • *Estimated enrolment.

  • †Enrolment not specified.

  • BET, bromodomain and extraterminal; FU, fluorouracil; MOS, medium overall survival; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; VPA, valproate.