Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urinary Bladder Diseases

Ureteral Diseases

Ureteral Neoplasms

Pelvic Neoplasms

Urethral Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Male Urogenital Diseases

Urethral Diseases

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

Dose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).

Dose Expansion: Enzalutamide at recommended dose level with standard doses of cisplatin and gemcitabine.

Enzalutamide orally once a day. Dose Escalation Level 1: 80 mg; Level 2: 160 mg. Dose Expansion at recommended dose level, after dose escalation.

Enzalutamide

Cisplatin at 70 mg/m\^2 IV on day 1, repeated every 21 days for total of 6 cycles.

Gemcitabine at 1000 mg/m\^2 IV on days 1, 8, repeated every 21 days for total of 6 cycles.

Jingsong Zhang, M.D., Ph.D.

Shilpa Gupta, M.D.

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.

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.

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

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 enzalutamide in 21 days due to study drug related toxicity.
* Missed day 8 dose of gemcitabine in cycle 1 will not be considered DLT.
* Delay of greater than 3 weeks from scheduled date in initiating cycle 2 due to study drug related toxicity.
* Discontinuation of a patient due to study drug related toxicity before completing cycle 1.

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.

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).

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.

H. Lee Moffitt Cancer Center and Research Institute

Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.

Dose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).

Dose Escalation: Dose Level 1

Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).

Dose Escalation: Level 2 Dose

Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.

Dose Expansion

Dose Escalation: Level 1 Dose

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

White Non-Hispanic

Black or African American

Asian

Hispanic or Latino

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

This study did not meet the anticipated accrual goal of 24 participants.

Dr. Jingsong Zhang

Dose Escalation

Recommended Dose of Enzalutamide

Partial Response

Progressive Disease

Stable Disease

Complete Response

Not Evaluable

Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).

All participants evaluable at time of analysis.

Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR)

Progression Free Survival (PFS)

Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).

Overall Survival (OS)

Dose Escalation- Level 2 Dose

Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer	NCT02300610	Bladder Cancer Carcinoma, Tran... Renal Pelvis Ca... Ureter Cancer Urethra Cancer	Enzalutamide Cisplatin Gemcitabine	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer	NCT02300610	Bladder Cancer Carcinoma, Tran... Renal Pelvis Ca... Ureter Cancer Urethra Cancer	Enzalutamide Cisplatin Gemcitabine	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

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