A feasibility study of combined epigenetic and vaccine therapy in advanced colorectal cancer with pharmacodynamic endpoint.
Adult
Aged
Aged, 80 and over
Azacitidine
/ administration & dosage
Biopsy
Cancer Vaccines
/ administration & dosage
Colorectal Neoplasms
/ drug therapy
Combined Modality Therapy
/ methods
DNA (Cytosine-5-)-Methyltransferase 1
/ antagonists & inhibitors
DNA Methylation
/ drug effects
Epigenomics
/ methods
Feasibility Studies
Female
Granulocyte-Macrophage Colony-Stimulating Factor
/ metabolism
Humans
Immunotherapy
/ methods
Immunotherapy, Active
/ methods
Leukocyte Common Antigens
/ drug effects
Male
Middle Aged
Safety
Severity of Illness Index
Tumor Microenvironment
Colorectal cancer
Epigenetic therapy
GVAX
Immunotherapy
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
02 02 2021
02 02 2021
Historique:
received:
24
11
2020
accepted:
13
01
2021
entrez:
3
2
2021
pubmed:
4
2
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Epigenetic therapies may modulate the tumor microenvironment. We evaluated the safety and optimal sequence of combination DNA methyltransferase inhibitor guadecitabine with a granulocyte macrophage-colony-stimulating-factor (GM-CSF) secreting colon cancer (CRC) vaccine (GVAX) using a primary endpoint of change in CD45RO + T cells. 18 patients with advanced CRC enrolled, 11 underwent paired biopsies and were evaluable for the primary endpoint. No significant increase in CD45RO + cells was noted. Grade 3-4 toxicities were expected and manageable. Guadecitabine + GVAX was tolerable but demonstrated no significant immunologic activity in CRC. We report a novel trial design to efficiently evaluate investigational therapies with a primary pharmacodynamic endpoint.Trial registry Clinicaltrials.gov: NCT01966289. Registered 21 October, 2013.
Identifiants
pubmed: 33531075
doi: 10.1186/s13148-021-01014-8
pii: 10.1186/s13148-021-01014-8
pmc: PMC7856736
doi:
Substances chimiques
Cancer Vaccines
0
GVAX vaccine
0
guadecitabine
2KT4YN1DP7
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
DNMT1 protein, human
EC 2.1.1.37
Leukocyte Common Antigens
EC 3.1.3.48
Azacitidine
M801H13NRU
Banques de données
ClinicalTrials.gov
['NCT01966289']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
25Subventions
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
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