Trial Outcomes & Findings for Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer (NCT NCT02300610)

Last Updated: 2019-08-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2019-08-01

Participant Flow

Participants were recruited at Moffitt Cancer Center and the University of Minnesota Masonic Cancer Center, February 2015 through August 2017.

Participant milestones

Participant milestones
Measure	Dose Escalation: Level 1 Dose Dose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation- Level 2 Dose Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Overall Study STARTED	3	3	4
Overall Study COMPLETED	2	3	3
Overall Study NOT COMPLETED	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation: Level 1 Dose Dose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation- Level 2 Dose Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Overall Study Withdrawal by Subject	1	0	1

Baseline Characteristics

Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation: Level 1 Dose n=3 Participants Dose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation: Level 2 Dose n=3 Participants Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion n=4 Participants Dose Expansion: Enzalutamide at recommended dose level with standard doses of cisplatin and gemcitabine.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Age, Continuous	65 years n=5 Participants	66.6 years n=7 Participants	65 years n=5 Participants	65.5 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized White Non-Hispanic	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	10 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: All participants in Dose Escalation arm.

Outcome measures

Outcome measures
Measure	Dose Escalation n=6 Participants Dose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation: Level 2 Dose Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Recommended Dose of Enzalutamide	160 mg	—	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All participants evaluable at time of analysis.

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.

Outcome measures

Outcome measures
Measure	Dose Escalation n=3 Participants Dose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation: Level 2 Dose n=3 Participants Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion n=4 Participants Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) Partial Response	0 Participants	3 Participants	1 Participants
Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) Progressive Disease	1 Participants	0 Participants	0 Participants
Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) Stable Disease	1 Participants	0 Participants	1 Participants
Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) Complete Response	0 Participants	0 Participants	1 Participants
Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) Not Evaluable	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 14 months

Population: All Participants.

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).

Outcome measures

Outcome measures
Measure	Dose Escalation n=3 Participants Dose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation: Level 2 Dose n=3 Participants Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion n=4 Participants Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Progression Free Survival (PFS)	3.81 months Interval 1.45 to 4.14	14.63 months Interval 13.71 to 15.88	7.68 months Interval 6.25 to 10.03

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dose Escalation n=3 Participants Dose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation: Level 2 Dose n=3 Participants Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion n=4 Participants Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Overall Survival (OS)	4.14 months Interval 3.81 to 10.59	14.63 months Interval 13.71 to 22.09	10.03 months Interval 6.25 to 20.05

Adverse Events

Dose Escalation: Dose Level 1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Dose Escalation: Level 2 Dose

Serious events: 3 serious events

Other events: 3 other events

Deaths: 3 deaths

Dose Expansion

Serious events: 3 serious events

Other events: 4 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Jingsong Zhang

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-3973

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose Escalation: Dose Level 1 n=3 participants at risk Dose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Escalation: Level 2 Dose n=3 participants at risk Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).	Dose Expansion n=4 participants at risk Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
Gastrointestinal disorders Nausea	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Gastrointestinal disorders Oral pain	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 2 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Gastrointestinal disorders Vomiting	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Infections and infestations Device related infection	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Infections and infestations Kidney infection	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Infections and infestations Lung infection	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Infections and infestations Urinary tract infection	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Investigations Creatinine increased	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Nervous system disorders Dysarthria	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Nervous system disorders Syncope	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Nervous system disorders Transient ischemic attacks	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	25.0% 1/4 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Psychiatric disorders Agitation	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Psychiatric disorders Confusion	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
Vascular disorders Thromboembolic event	33.3% 1/3 • Number of events 1 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/3 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.	0.00% 0/4 • 2 years, 7 months Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.