Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer
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|ClinicalTrials.gov Identifier: NCT02300610|
Recruitment Status : Active, not recruiting
First Posted : November 25, 2014
Last Update Posted : January 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer Carcinoma, Transitional Cell Renal Pelvis Cancer Ureter Cancer Urethra Cancer||Drug: Enzalutamide Drug: Cisplatin Drug: Gemcitabine||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/1b Study of Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer|
|Actual Study Start Date :||February 11, 2015|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2019|
Experimental: Dose Escalation and Dose Expansion
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.
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.
Other Name: Gemzar ®
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to 6 months ]
Dose Escalation. MTD of Enzalutamide when given with Cisplatin and Gemcitabine at standard doses.
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.
- Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) [ Time Frame: 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.
- Progression Free Survival (PFS) [ Time Frame: Up to 6 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).
- Overall Survival (OS) [ Time Frame: Up to 6 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02300610
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Minnesota|
|University of Minnesota, Masonic Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Jingsong Zhang, M.D., Ph.D.||H. Lee Moffitt Cancer Center and Research Institute|
|Study Chair:||Shilpa Gupta, M.D.||University of Minnesota Masonic Cancer Center|