Trial Outcomes & Findings for First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma (NCT NCT01215136)

Last Updated: 2023-11-24

Results Overview

To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

4 months

Results posted on

2023-11-24

Participant Flow

Participant milestones

Participant milestones
Measure	Everolimus Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Everolimus Plus Paclitaxel Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Overall Study STARTED	7	29
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	6	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Everolimus Plus Paclitaxel Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Overall Study Adverse Event	2	9
Overall Study Disease Progression	3	14
Overall Study Symptomatic Deterioration	1	1
Overall Study Death	0	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus n=7 Participants Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Everolimus Plus Paclitaxel n=29 Participants Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.	Total n=36 Participants Total of all reporting groups
Age, Continuous	78 years n=5 Participants	72.14 years n=7 Participants	73.28 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	22 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	28 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	27 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	29 participants n=7 Participants	36 participants n=5 Participants
Karnovsky Performance Status (KPS) at Screening KPS 100	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Karnovsky Performance Status (KPS) at Screening KPS 90	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants
Karnovsky Performance Status (KPS) at Screening KPS 80	0 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants
Karnovsky Performance Status (KPS) at Screening KPS 70	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Karnovsky Performance Status (KPS) at Screening KPS 60	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months

To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Cohort 2 n=29 Participants Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Response Rate of Single-Agent Everolimus and Everolimus + Paclitaxel	14.3 percentage of participants	37.9 percentage of participants

SECONDARY outcome

Timeframe: 5 months

To determine the safety of everolimus and everolimus plus paclitaxel in this patient population. A summary with the count of events per grade is provided.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Cohort 2 n=29 Participants Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Number of Adverse Events as a Measure of Safety and Tolerability Grade 1 Adverse Events	10 Number of Events	116 Number of Events
Number of Adverse Events as a Measure of Safety and Tolerability Grade 2 Adverse Events	9 Number of Events	75 Number of Events
Number of Adverse Events as a Measure of Safety and Tolerability Grade 3 Adverse Events	4 Number of Events	39 Number of Events
Number of Adverse Events as a Measure of Safety and Tolerability Grade 4 Adverse Events	0 Number of Events	1 Number of Events
Number of Adverse Events as a Measure of Safety and Tolerability Grade 5 Adverse Events	0 Number of Events	3 Number of Events

SECONDARY outcome

Timeframe: 4 months

To determine median progression free survival per RECIST 1.1, per cohort.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Cohort 2 n=29 Participants Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Progression Free Survival	2.3327 months Interval 1.6099 to 3.5483	5.8480 months Interval 2.9569 to 7.655

SECONDARY outcome

Timeframe: 12 months

To determine median overall survival at 1-year from the initiation of treatment.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Cohort 2 n=29 Participants Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Overall Survival	4.5010 months Interval 2.2341 to 8.3121	10.8747 months Interval 6.8337 to 14.3573

Adverse Events

Cohort 1

Serious events: 1 serious events

Other events: 5 other events

Deaths: 7 deaths

Cohort 2

Serious events: 11 serious events

Other events: 28 other events

Deaths: 25 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 n=7 participants at risk Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance \< 60 ml/min AND Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.	Cohort 2 n=29 participants at risk Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance \< 60 ml/min OR Karnofsky performance status of 60-70%) Everolimus: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis. Paclitaxel: Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Infections and infestations INFECTIONS AND INFESTATIONS - OTHER, SPECIFY	14.3% 1/7 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	6.9% 2/29 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Metabolism and nutrition disorders DEHYDRATION	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Gastrointestinal disorders DIARRHEA	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Respiratory, thoracic and mediastinal disorders DYSPNEA	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
General disorders EDEMA LIMBS	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Musculoskeletal and connective tissue disorders GENERALIZED MUSCLE WEAKNESS	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Hepatobiliary disorders HEPATOBILIARY DISORDERS - OTHER, SPECIFY	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Infections and infestations LUNG INFECTION	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	6.9% 2/29 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Respiratory, thoracic and mediastinal disorders RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Vascular disorders THROMBOEMBOLIC EVENT	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	3.4% 1/29 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.	6.9% 2/29 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 12 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.

Other adverse events

Additional Information

Clinicaltrials.gov Results Coordinator

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place