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COMPLETEDPHASE1

Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

A Phase I/1b Study of Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

NCT02300610•H. Lee Moffitt Cancer Center and Research Institute

Summary

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.

Detailed Description

For the phase 1 dose escalation phase, the starting dose of enzalutamide will be 80 mg orally once a day (Level 1). The dosing regimen of cisplatin and gemcitabine will be at standard doses of Gemcitabine at 1000 mg/m\^2 IV on days 1, 8 and cisplatin at 70 mg/m2 IV on day 1, repeated every 21 days for total of 6 cycles. Three patients will be treated dose level 1 (enzalutamide 80 mg daily). If 0 patients experience dose limiting toxicity (DLT), dose escalation will be done to level 2 of enzalutamide 160 mg daily. If 1 patient experiences DLT, 3 more patients will be treated at the same dose level; if 1 of 6 experiences DLT, escalate the dose to next level, and if 2 or more of 6 experiences DLT, the dose level 1 (80 mg enzalutamide) will be the recommended dose for dose expansion cohort. The cohort expansion will then be done by enrolling 12 patients with stage IV bladder cancer, who express androgen receptor (AR) staining of 1+ and above by immunohistochemistry (IHC), to determine the safety and tolerability of cisplatin and gemcitabine with the recommended dose level of enzalutamide (80 mg or 160 mg, depending upon the safety results from dose escalation part) in this expanded cohort of patients with AR + bladder cancer. Enzalutamide would be continued after completion of 6 cycles of gemcitabine-cisplatin for patients exhibiting a response or stable disease, until they experience disease progression.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Cytologically or histologically confirmed evidence of transitional cell carcinoma of bladder, renal pelvis, ureter or urethra.
•Patients with Stage IV (locally advanced or metastatic) disease. Must have measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST).
•Minimum of 4 weeks since any major surgery, completion of radiation.
•Prior treatment with cytotoxic chemotherapy is not a requirement, but allowed only if used in neoadjuvant, adjuvant or for bladder preserving protocols, as long as was administered \> 6 months prior to starting study.
•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
•Life expectancy 12 weeks or more.
•Must have normal organ and marrow function.
•Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating.
•Sexually active women of childbearing age and men should be willing to follow birth control guidelines.
•Should be able to swallow enzalutamide and comply with study requirements.

Exclusion Criteria

•Prior treatment with any cytotoxic chemotherapy in metastatic setting. Prior treatment with cytotoxic chemotherapy is allowed only if used in neoadjuvant, adjuvant or for bladder preserving protocols, as long as was administered \> 6 months prior to starting study.
•Have undergone major surgery within 4 weeks prior to study enrollment.
•Chronic treatment with steroids or any other immunosuppressant drugs.
•Should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.
•History of seizures, predisposing factors for seizures, including underlying brain injury with loss of consciousness within previous 12 months, transient ischemic attack within previous 12 months, cerebral vascular accident or brain arteriovenous malformation.
•Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
•Congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the 6 months preceding enrollment.
•Known history of HIV.
•Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
•Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice birth control guidelines.
+7 more criteria

Locations (2)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, United States

Key Dates

Start Date

February 11, 2015

Primary Completion Date

August 7, 2017

Completion Date

April 19, 2019

Last Updated

August 1, 2019

Enrollment

ACTUAL participants

Conditions

Bladder CancerCarcinoma, Transitional CellRenal Pelvis CancerUreter CancerUrethra Cancer

Interventions

Enzalutamide

DRUG

Cisplatin

DRUG

Gemcitabine

DRUG

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RECRUITING

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: August 1, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

Inclusion Criteria

Exclusion Criteria

Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial

Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease

En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device

Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes

Comprehensive Multimodal Prehabilitation Alone or With Neoadjuvant Therapy Before Major Cancer Surgery

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)