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NCT02099864

Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

Completed Phase 2 Results posted Last updated 19 September 2024
What this trial tests

Phase 2 trial testing Enzalutamide in Castration-Resistant Prostate Carcinoma in 36 participants. Completed in 8 July 2024.

Timeline
5 February 2014
Primary endpoint
1 October 2019
8 July 2024

Quick facts

Lead sponsorOHSU Knight Cancer Institute
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment36
Start date5 February 2014
Primary completion1 October 2019
Estimated completion8 July 2024
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

OHSU Knight Cancer Institute

Who can join

18 and older, male only, with Castration-Resistant Prostate Carcinoma or Metastatic Malignant Neoplasm in the Bone. 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.

Percentage of Participants With a >= 50% Decline in Prostate-specific Antigen (PSA) Value Primary · Baseline to 12 weeks

The percentage of participants with a \>= 50% decline in PSA values will be reported with 95% exact confidence interval. For each participant, percentage decline in PSA values are calculated as 100% times the difference between PSA values taken at baseline and 12 weeks divided by PSA values at baseline. Percentage of participants determined as 100% times the number of participants with \>= 50% decline divided by overall number of participants.

GroupValue95% CI
Treatment (Enzalutamide)73.555.6 – 87.1
Percentage of Participants With Tumor Protein 53 Gene (TP53) Copy Number Alterations and Mutations Primary · Baseline to 12 weeks

Evaluate the association between PSA response at 12 weeks after initiating therapy, and TP53 copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with TP53 copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

GroupValue95% CI
Responders28.6
PSA Non-responders80.0
Percentage of Participants With Phosphatase and Tensin Homologue Gene (PTEN) Copy Number Alterations and Mutations Primary · Baseline to 12 weeks

Evaluate the association between PSA response at 12 weeks after initiating therapy, and PTEN copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with PTEN copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

GroupValue95% CI
Responders47.6
PSA Non-responders40.0
Percentage of Participants With Retinoblastoma Gene (RB1) Copy Number Alterations and Mutations Primary · Baseline to 12 weeks

Evaluate the association between PSA response at 12 weeks after initiating therapy, and RB1 copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with RB1 copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

GroupValue95% CI
Responders9.5
PSA Non-responders0.0
Androgen Receptor (AR) Messenger RNA (mRNA) Expression Primary · Baseline to 12 weeks

Median AR mRNA expression between responders and non-responders.

GroupValue95% CI
Responders224.9± 133.2
Non-responders201.7± 201.7
Androgen Receptor Variant 7 (AR-V7) Expression Primary · Baseline to 12 weeks

Median AR-V7 expression between responders and non-responders.

GroupValue95% CI
Responders10.4± 7.2
Non-responders12.3± 11.8
Percentage of Participants With Androgen Receptor (AR) Copy Number Alterations and Mutations Primary · Baseline to 12 weeks

Evaluate the association between PSA response at 12 weeks after initiating therapy, and AR copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with AR copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

GroupValue95% CI
Responders73.7
PSA Non-responders100.0
Number of Participants With Protein Expression of AR Primary · Baseline to 12 weeks

The number of participants, responders and non-responders, that were found to have protein expression of AR.

GroupValue95% CI
Responders15
PSA Non-responders6
Androgen Receptor (AR) Activity Level Primary · Baseline to 12 weeks

Median Normalized Enrichment Score (NES) AR activity levels of responders and non-responders. Gene Set Enrichment Analysis (GSEA) is used to interpret gene expression data. GSEA enrichment score (ES) reflects the degree to which a gene set (GS) is overrepresented at the top or bottom of a ranked list of genes. ES is calculated by walking down the list, increasing a running-sum statistic when a gene is in the GS and decreasing when it's not. Magnitude of increment depends on correlation of the gene with the phenotype. ES is the max deviation from zero encountered in walking the list. Positive E

GroupValue95% CI
Responders2.2± 3.3
Non-responders-2.6± 1.4
Prostate-specific Antigen (PSA) Changes Secondary · Baseline to up to 5 years

Number of patients who achieved a 50% or greater PSA decline any time after 12 weeks post-baseline.

GroupValue95% CI
Treatment (Enzalutamide)25
Percentage of Participants With an Objective Response Secondary · Baseline to date of first documented radiographic objective response, assessed up to 1 year

The percentage of participants with an objective response will be reported with 95% exact confidence interval. Objective radiographic response is evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. For each participant, objective response is calculated as 100% times the difference between the sum of measurable target lesio

GroupValue95% CI
Treatment (Enzalutamide)63.640.7 – 82.8
Progression-free Survival (PFS) Secondary · Time from day 1 of study drug treatment to date of first documented radiographic progression or clinical progression, assessed up to 5 years

Correlations between baseline molecular features and pathways and PFS will be assessed using cox regression model. In addition, Kaplan-Meier plots will be used to graphically illustrate the survival distributions across the strata of categorical molecular predictors.

GroupValue95% CI
Responders23.910.9 – 33.6
PSA Non-responders3.72.0 – 11.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Enzalutamide)
Serious: 6/36 (17%)
Deaths: 2/36

Serious adverse events (15 terms)

ReactionSystemTreatment (Enzalutamide)
Urinary tract infectionInfections and infestations
fractureInjury, poisoning and procedural complications
Acute kidney injuryRenal and urinary disorders
AnemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progressionGeneral disorders
Heart failureCardiac disorders
HematuriaRenal and urinary disorders
HypotensionVascular disorders
Intracranial hemorrhageNervous system disorders
EncephalopathyNervous system disorders
Renal and urinary disorders - other, kidney cancerRenal and urinary disorders
SepsisInfections and infestations
Soft tissue infectionInfections and infestations
Other adverse events (34 terms — click to expand)

ReactionSystemTreatment (Enzalutamide)
fatigueGeneral disorders
fallInjury, poisoning and procedural complications
fractureInjury, poisoning and procedural complications
painGeneral disorders
Musculoskeletal and connective tissue disorder - Other, hip painMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Upper respiratory infectionInfections and infestations
dizzinessNervous system disorders
dyspneaRespiratory, thoracic and mediastinal disorders
edema limbsGeneral disorders
Hot flashesVascular disorders
StrokeNervous system disorders
Urinary tract infectionInfections and infestations
depressionPsychiatric disorders
diarrheaGastrointestinal disorders
DysgeusiaNervous system disorders
GynecomastiaReproductive system and breast disorders
HematuriaRenal and urinary disorders
HypertensionVascular disorders
HypokalemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Nervous system disorders - Other, neuropathyNervous system disorders
back painMusculoskeletal and connective tissue disorders
ParesthesiaNervous system disorders
MyalgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, shoulder painMusculoskeletal and connective tissue disorders
PresyncopeNervous system disorders
PruritusSkin and subcutaneous tissue disorders
Skin infectionInfections and infestations
Urinary incontinenceRenal and urinary disorders
Urinary retentionRenal and urinary disorders
Weight lossInvestigations

Most-reported serious reactions: Urinary tract infection, fracture, Acute kidney injury, Anemia, Atrial fibrillation, Myelodysplastic syndrome, Disease progression, Heart failure.

Data from ClinicalTrials.gov NCT02099864 adverse events section.

Sponsor's own description

This phase II trial studies genetic and molecular mechanisms in assessing response in patients with prostate cancer receiving enzalutamide therapy. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of androgens made by the body. Studying samples of tissue and blood in the laboratory from patients with prostate cancer may help doctors better understand castration-resistant prostate cancer. It may also help doctors make improvements in prostate cancer treatment.

Publications & conference data

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

  1. Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.
    Alumkal JJ, Sun D, Lu E, Beer TM, et al · · 2020 · cited 125× · PMID 32424106 · DOI 10.1073/pnas.1922207117
  2. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.
    Bryce AH, Alumkal JJ, Armstrong A, Higano CS, et al · · 2017 · cited 84× · PMID 28117385 · DOI 10.1038/pcan.2016.71
  3. Epithelial-Mesenchymal Transition Signaling and Prostate Cancer Stem Cells: Emerging Biomarkers and Opportunities for Precision Therapeutics.
    Chaves LP, Melo CM, Saggioro FP, Reis RBD, et al · · 2021 · cited 45× · PMID 34946849 · DOI 10.3390/genes12121900
  4. Recent Advances in Liquid Biopsy in Patients With Castration Resistant Prostate Cancer.
    Di Nunno V, Gatto L, Santoni M, Cimadamore A, et al · · 2018 · cited 15× · PMID 30319966 · DOI 10.3389/fonc.2018.00397
  5. Integrative molecular network analysis identifies emergent enzalutamide resistance mechanisms in prostate cancer.
    King CJ, Woodward J, Schwartzman J, Coleman DJ, et al · · 2017 · cited 10× · PMID 29340039 · DOI 10.18632/oncotarget.22560
  6. Redefining cancer care: harnessing circulating tumor cells' potential for improved diagnosis and prognosis.
    Janjua D, Chaudhary A, Joshi U, Tripathi T, et al · · 2025 · cited 4× · PMID 40676582 · DOI 10.1186/s12935-025-03883-y
  7. BET inhibitors reduce tumor growth in preclinical models of gastrointestinal gene signature-positive castration-resistant prostate cancer.
    Shukla S, Li D, Cho WH, Schoeps DM, et al · · 2025 · cited 2× · PMID 40553565 · DOI 10.1172/jci180378
  8. Transcriptional profiling clarifies a program of enzalutamide extreme non-response in lethal prostate cancer.
    Kumaraswamy A, Hu YM, Yates JA, Zhang C, et al · · 2025 · PMID 40624104 · DOI 10.1038/s41698-025-01002-8

Verify or expand the search:

Other trials of Enzalutamide

Trials testing the same drug.

Other recruiting trials for Castration-Resistant Prostate Carcinoma

Currently open trials in the same condition.

Other OHSU Knight Cancer Institute trials

Trials by the same sponsor.

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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/NCT02099864.

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