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NCT03322384

UCDCC#271: Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma

Completed Phase 1, PHASE2 Results posted Last updated 1 February 2022
What this trial tests

Phase 1, PHASE2 trial testing epacadostat in Advanced Solid Tumors in 20 participants. Completed in 8 April 2020.

Timeline
17 January 2018
Primary endpoint
24 February 2020
8 April 2020

Quick facts

Lead sponsorUniversity of California, Davis
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment20
Start date17 January 2018
Primary completion24 February 2020
Estimated completion8 April 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of California, Davis

Who can join

18 and older, any sex, with Advanced Solid Tumors or Lymphoma. 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.

Maximum Tolerated Dose (MTD) Primary · Up to 30 days of treatment

To determine the maximum tolerated dose (MTD) of epacadostat that can be given with radiotherapy and intralesional SD-101 immunotherapy for the phase I portion of the study. The MTD will be determined using a standard 3+3 design. Patients will be monitored weekly during a 30-day dose-limiting toxicity (DLT) period. MTD can be defined as The maximum dose at which \<2 of 6 patients experienced a DLT.

GroupValue95% CI
Experimental300
Incidence of Related Adverse Events [Safety and Tolerability] Primary · Through study completion, an average of one year

To characterize the safety profile of this regimen using CTCAE v4.03 (Common Toxicity Criteria for Adverse Events version 4.03) in the phase II expansion . The expansion phase (phase II) will be conducted using the MTD defined as the highest dose at which no more than one of six patients develops a DLT or Dose Level 1 if the MTD is not reached. Patients will be monitored every week during the first 30 days of study and then monthly thereafter up to a period of 1 year.

GroupValue95% CI
Experimental17
Abscopal Response Rate Secondary · Through study completion, an average of one year

Abscopal Response Rate (ARR) is defined as objective response rate (the percentage of patient that achieve a partial or complete response) at unirradiated sites using irRECIST criteria using imaging obtained every 60 days during the 1 year study period.

GroupValue95% CI
Experimental4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 1 year.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experimental
Serious: 9/20 (45%)
Deaths: 10/20

Serious adverse events (11 terms)

ReactionSystemExperimental
Gastrointestinal disorders - Other, specify: lower GI bleedGastrointestinal disorders
SepsisInfections and infestations
Upper respiratory infectionInfections and infestations
Investigations - Other, specify: transanimitisInvestigations
HyponatremiaMetabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify: electrolyte and fluid disorderMetabolism and nutrition disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Muscle weakness lower limbMusculoskeletal and connective tissue disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify:disease progresNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injuryRenal and urinary disorders
Urinary retentionRenal and urinary disorders
Other adverse events (32 terms — click to expand)

ReactionSystemExperimental
NauseaGastrointestinal disorders
FatigueGeneral disorders
Lymphocyte count decreasedInvestigations
VomitingGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
Edema limbsGeneral disorders
White blood cell decreasedInvestigations
AnemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Injection site reactionGeneral disorders
HeadacheNervous system disorders
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
DiarrheaGastrointestinal disorders
Alkaline phosphatase increasedInvestigations
DehydrationMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
Sinus tachycardiaCardiac disorders
DysphagiaGastrointestinal disorders
ChillsGeneral disorders
Weight lossInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
DysgeusiaNervous system disorders
ParesthesiaNervous system disorders
ConfusionPsychiatric disorders
DepressionPsychiatric disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders

Most-reported serious reactions: Gastrointestinal disorders - Other, specify: lower GI bleed, Sepsis, Upper respiratory infection, Investigations - Other, specify: transanimitis, Hyponatremia, Metabolism and nutrition disorders - Other, specify: electrolyte and fluid disorder, Generalized muscle weakness, Muscle weakness lower limb.

Data from ClinicalTrials.gov NCT03322384 adverse events section.

Sponsor's own description

Checkpoint blockade immunotherapy has revolutionized the management of a variety of advanced malignancies. Monoclonal antibodies targeting the PD-1 / PD-L1 interaction have received FDA approvals for non-small cell lung cancer, melanoma, Merkel cell carcinoma, renal cell carcinoma, hepatocellular, squamous cell carcinoma of the head and neck, microsatellite instability high colorectal carcinoma, urothelial carcinoma, and classical Hodgkin's lymphoma. Despite the promising evidence for deep and durable responses with these agents, the majority of patients either fail to respond or develop resistance to treatment. Thus, there is interested in developing alternative immunotherapeutic strategies. The investigators hypothesize that a novel immunotherapeutic combination of radiotherapy (RT) with intralesional CpG and indolamine-2,3-dioxygenase blockade may offer significant clinical benefit to patients and proposing a microtrial testing this combination for advanced/refractory solid tumors and lymphoma.

Publications & conference data

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

  1. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy.
    Tang K, Wu YH, Song Y, Yu B. · · 2021 · cited 276× · PMID 33883013 · DOI 10.1186/s13045-021-01080-8
  2. Trial Watch: Toll-like receptor agonists in cancer immunotherapy.
    Smith M, García-Martínez E, Pitter MR, Fucikova J, et al · · 2018 · cited 171× · PMID 30524908 · DOI 10.1080/2162402x.2018.1526250
  3. Recent Advances in Oligonucleotide Therapeutics in Oncology.
    Xiong H, Veedu RN, Diermeier SD. · · 2021 · cited 132× · PMID 33804856 · DOI 10.3390/ijms22073295
  4. Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives.
    Mukherjee S, Patra R, Behzadi P, Masotti A, et al · · 2023 · cited 102× · PMID 37822929 · DOI 10.3389/fimmu.2023.1244345
  5. Toll-like receptor 9 agonists and combination therapies: strategies to modulate the tumour immune microenvironment for systemic anti-tumour immunity.
    Dongye Z, Li J, Wu Y. · · 2022 · cited 92× · PMID 35902641 · DOI 10.1038/s41416-022-01876-6
  6. Lifting the innate immune barriers to antitumor immunity.
    Rothlin CV, Ghosh S. · · 2020 · cited 63× · PMID 32273348 · DOI 10.1136/jitc-2020-000695
  7. Immune checkpoint inhibitors in lymphoma: challenges and opportunities.
    Hatic H, Sampat D, Goyal G. · · 2021 · cited 50× · PMID 34277837 · DOI 10.21037/atm-20-6833
  8. Immunotherapy and pancreatic cancer: unique challenges and potential opportunities.
    Young K, Hughes DJ, Cunningham D, Starling N. · · 2018 · cited 49× · PMID 30574212 · DOI 10.1177/1758835918816281

Verify or expand the search:

Other trials of epacadostat

Trials testing the same drug.

Other recruiting trials for Advanced Solid Tumors

Currently open trials in the same condition.

Other University of California, Davis trials

Trials by the same sponsor.

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