Compound | Epigenetic target | Combination | Treatment | NCT number | Outcome measures | Results in PDAC | Enrolled tumour entities | No. of enrolled patients |
---|---|---|---|---|---|---|---|---|
Phase I and combined phase I/II | ||||||||
Vorinostat | HDAC class I/II | Marizomib | Palliative | 00667082 | MTD, pharmacokinetics, pharmacodynamics, toxicity and antitumour activity of the combination therapy | No antitumour activity | PDAC, NSCLC Multiple myeloma Melanoma Lymphoma | 22 |
Vorinostat | HDAC class I/II | Radiation capecitabine | Palliative+adjuvant | 00983268 | MTD, tumour response, toxicity | No results yet | Periampullary adenocarcinoma PDAC | 21 |
Vorinostat | HDAC class I/II | Radiation 5-FU | Palliative | 00948688 | MTD, progression-free survival 7 months after registration | No results yet | PDAC | 50* |
Vorinostat | HDAC class I/II | Radiation | Palliative | 00831493 | MTD, MOS, correlation of serum cytokine levels with symptoms and outcome | No results yet | PDAC | 3 |
Valproate | HDAC class I | Epirubicin 5-FU cyclophosphamide | Palliative | 00246103 | Safety, tolerability, MTD, pharmacokinetic profile, VPA effect on histone acetylation in blood cells and tumour biopsies | Low potency, but preferable toxicity profile, might be beneficial for patients with HDAC2 overexpression | Advanced neoplasms | 44 |
Entinostat | HDAC class I | 13-cis retinoic acid | Palliative | 00098891 | MTD, dose-limiting toxicity, pharmacokinetics, tumour response | Stable disease in one patient with chemotherapy-resistant PDAC | Metastatic or advanced solid tumours or lymphomas | 24 |
Entinostat | HDAC class I | Palliative | 00020579 | MTD and dose-limiting toxicity, pharmacokinetics, acetylation in blood cells, tumour response | No results yet | Not specified cancer | 75* | |
Mocetinostat | HDAC classes I+IV | Gemcitabine | Palliative | 00372437 | Phase 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 disease | Solid tumours where gemcitabine is considered as standards of care, phase II limited to PDAC | 47 |
CHR-3996 | HDAC class I | Palliative | 00697879 | Safety, tolerability, dose-limiting toxicity, MTD, pharmacokinetics, antitumour activity | Reduction of liver metastases in one patient with acinar pancreatic cancer | Solid tumours | 40 | |
Romidepsin | HDAC class I | Gemcitabine | Palliative | 00379639 | Dose-limiting toxicity, number of patients with adverse events, best overall response | 4/9 patients showed stable disease; additive haematological side effects | Solid tumours | 36 |
OTX015 | Pan-BET | Palliative | 02259114 | Number of dose-limiting toxicities at cycle 1 | No results yet | NUT midline carcinoma Breast cancer NSCLC, castrate-resistant prostate cancer, PDAC | 98* | |
Bay1238097 | Pan-BET | Palliative | 02369029 | Incidence of dose-limiting toxicity, tumour response | No results yet | Neoplasms | 8 | |
BI-2536 | BRD4 | Gemcitabine | Palliative | 02215044 | Occurrence of dose-limiting toxicity, survival, tumour response, CA19-9 levels, maximal concentration of the analytes in plasma | No results yet | Pancreatic neoplasms | 12 |
Phase II non-radomised | ||||||||
Panobinostat | HDAC class I/II | Bortezomib | Palliative | 01056601 | PFS, number of participants with tumour response, duration of response, characterisation of quality and quantity toxicity | No treatment response and severe treatment-related toxicity, study was closed ahead of schedule | PDAC | 7 |
Curcumin | p300, CBP | Gemcitabine | Palliative | 00192842 | Time to tumour progression, response rate, survival, clinical benefit, toxicity | In chemotherapy-naïve patients with advanced PDAC. Increased GI toxicity | PDAC | 17 |
Curcumin | p300, CBP | Palliative | 00094445 | 6 months survival, response rate, assessment of biological activity in blood mononuclear cells via signalling and apoptotic pathways, pharmacokinetics | No severe toxicity, curcumin showed biological activity with stable disease (1/22) and brief response (1/22) with 73% reduction of liver metastasis size | PDAC | 50 | |
BI-2536 | BRD4 | Palliative | 00710710 | Objective response, PFS, dose-limiting toxicity, overall survival, clinical benefit response | First-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 initiated | Pancreatic neoplasms | 89 | |
Phase II randomised | ||||||||
CI-994 | HDAC class I | Gemcitabine | Palliative | 00004861 | Efficiency and safety of CI-994 in combination with gemcitabine | Inferior compared with gemcitabine monotherapy with decreased quality of life | PDAC | † |
*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.