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NCT02300610

Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

Completed Phase 1 Results posted Last updated 1 August 2019
What this trial tests

Phase 1 trial testing Enzalutamide in Bladder Cancer in 10 participants. Completed in 19 April 2019.

Timeline
11 February 2015
Primary endpoint
7 August 2017
19 April 2019

Quick facts

Lead sponsorH. Lee Moffitt Cancer Center and Research Institute
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment10
Start date11 February 2015
Primary completion7 August 2017
Estimated completion19 April 2019
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Who can join

18 and older, any sex, with Bladder Cancer or Carcinoma, Transitional Cell. 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.

Recommended Dose of Enzalutamide Primary · Up to 6 months

Dose Escalation. Maximum Tolerated Dose (MTD) of Enzalutamide when given with Cisplatin and Gemcitabine at standard doses. Dose Level 1: 80 mg Enzalutamide; Dose Level 2: 160 mg Enzalutamide. Dose-Limiting Toxicity (DLT) is defined as any of the following occurring in the first 21 days (cycle 1) of study participation that are considered at least possibly related to enzalutamide administration. Toxicities that are in the opinion of the investigator(s) attributable exclusively to gemcitabine or cisplatin will not be considered DLT. * 7 consecutive missed doses (out of 21 doses) of enzalutamid

GroupValue95% CI
Dose Escalation160
Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) Secondary · Up to 6 months

Dose Expansion. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Partial Response
GroupValue95% CI
Dose Escalation: Level 1 Dose0
Dose Escalation: Level 2 Dose3
Dose Expansion1
Progressive Disease
GroupValue95% CI
Dose Escalation: Level 1 Dose1
Dose Escalation: Level 2 Dose0
Dose Expansion0
Stable Disease
GroupValue95% CI
Dose Escalation: Level 1 Dose1
Dose Escalation: Level 2 Dose0
Dose Expansion1
Complete Response
GroupValue95% CI
Dose Escalation: Level 1 Dose0
Dose Escalation: Level 2 Dose0
Dose Expansion1
Not Evaluable
GroupValue95% CI
Dose Escalation: Level 1 Dose1
Dose Escalation: Level 2 Dose0
Dose Expansion1
Progression Free Survival (PFS) Secondary · 14 months

Dose Expansion. PFS is defined as the time from randomization until objective tumor progression or death. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

GroupValue95% CI
Dose Escalation: Level 1 Dose3.811.45 – 4.14
Dose Escalation: Level 2 Dose14.6313.71 – 15.88
Dose Expansion7.686.25 – 10.03
Overall Survival (OS) Secondary · Up to 24 Months

Dose Expansion. Overall survival is defined as the time from randomization until death from any cause, and is measured in the intent-to-treat population.

GroupValue95% CI
Dose Escalation: Level 1 Dose4.143.81 – 10.59
Dose Escalation: Level 2 Dose14.6313.71 – 22.09
Dose Expansion10.036.25 – 20.05

Adverse events — posted to ClinicalTrials.gov

Time frame: 2 years, 7 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Escalation: Dose Level 1
Serious: 2/3 (67%)
Deaths: 3/3
Dose Escalation: Level 2 Dose
Serious: 3/3 (100%)
Deaths: 3/3
Dose Expansion
Serious: 3/4 (75%)
Deaths: 2/4

Serious adverse events (23 terms)

ReactionSystemDose Escalation: Dose Leve…Dose Escalation: Level 2 D…Dose Expansion
NauseaGastrointestinal disorders
Oral painGastrointestinal disorders
PancreatitisGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
Device related infectionInfections and infestations
Kidney infectionInfections and infestations
Lung infectionInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Creatinine increasedInvestigations
DehydrationMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Neoplasms benign, malignant and unspecified - OtherNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DysarthriaNervous system disorders
SyncopeNervous system disorders
Transient ischemic attacksNervous system disorders
AgitationPsychiatric disorders
ConfusionPsychiatric disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Thromboembolic eventVascular disorders
Other adverse events (98 terms — click to expand)

ReactionSystemDose Escalation: Dose Leve…Dose Escalation: Level 2 D…Dose Expansion
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Platelet count decreasedInvestigations
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
White blood cell decreasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
HeadacheNervous system disorders
FeverGeneral disorders
Alkaline phosphatase increasedInvestigations
Creatinine increasedInvestigations
Weight lossInvestigations
AnorexiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypercalcemiaMetabolism and nutrition disorders
HypertriglyceridemiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
BloatingGastrointestinal disorders
Dry mouthGastrointestinal disorders
DizzinessNervous system disorders
DysgeusiaNervous system disorders
FallInjury, poisoning and procedural complications
HypotensionVascular disorders
HypertensionVascular disorders
TinnitusEar and labyrinth disorders
Edema limbsGeneral disorders
Non-cardiac chest painGeneral disorders
ChillsGeneral disorders
Infusion site extravasationGeneral disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Activated partial thromboplastin time prolongedInvestigations
Blood bilirubin increasedInvestigations
Electrocardiogram QT corrected interval prolongedInvestigations

Most-reported serious reactions: Nausea, Oral pain, Pancreatitis, Small intestinal obstruction, Vomiting, Device related infection, Kidney infection, Lung infection.

Data from ClinicalTrials.gov NCT02300610 adverse events section.

Sponsor's own description

The main purpose of this study is to find out the dose of enzalutamide that can be safely given with gemcitabine and cisplatin in patients with advanced bladder cancer. Researchers also want to find out the side effects of these drugs when given together. This study will also help in finding out the effect on tumor of the combination of enzalutamide, gemcitabine and cisplatin.

Publications & conference data

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

  1. Androgen Receptor Signaling in Bladder Cancer.
    Li P, Chen J, Miyamoto H. · · 2017 · cited 78× · PMID 28241422 · DOI 10.3390/cancers9020020
  2. Androgen receptor-regulated circFNTA activates KRAS signaling to promote bladder cancer invasion.
    Chen J, Sun Y, Ou Z, Yeh S, et al · · 2020 · cited 75× · PMID 32052578 · DOI 10.15252/embr.201948467
  3. AR-Signaling in Human Malignancies: Prostate Cancer and Beyond.
    Schweizer MT, Yu EY. · · 2017 · cited 45× · PMID 28085048 · DOI 10.3390/cancers9010007
  4. Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer.
    Wucherpfennig S, Rose M, Maurer A, Cassataro MA, et al · · 2021 · cited 29× · PMID 34768978 · DOI 10.3390/ijms222111547
  5. Androgen receptor in bladder cancer: A promising therapeutic target.
    Tripathi A, Gupta S. · · 2020 · cited 28× · PMID 32742928 · DOI 10.1016/j.ajur.2020.05.011
  6. Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy.
    Ide H, Miyamoto H. · · 2021 · cited 25× · PMID 34064926 · DOI 10.3390/cells10051169
  7. Mechanism of Sex Differences in Bladder Cancer: Evident and Elusive Sex-biasing Factors.
    Lam CM, Li Z, Theodorescu D, Li X. · · 2022 · cited 13× · PMID 36277328 · DOI 10.3233/blc-211658
  8. Roles of Androgen Receptor Signaling in Urothelial Carcinoma.
    Sundi D, Collier KA, Yang Y, Diaz DA, et al · · 2024 · cited 9× · PMID 38398136 · DOI 10.3390/cancers16040746

Verify or expand the search:

Other trials of Enzalutamide

Trials testing the same drug.

Other recruiting trials for Bladder Cancer

Currently open trials in the same condition.

Other H. Lee Moffitt Cancer Center and Research 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/NCT02300610.

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