Trial Outcomes & Findings for A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer (NCT NCT00942578)

Last Updated: 2018-10-11

Results Overview

The RP2D is the dose at which there are no dose-limiting toxicities (defined as a ≥grade 3 hematological toxicity related to lenalidomide).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

3 weeks

Results posted on

2018-10-11

Participant Flow

Participant milestones

Participant milestones
Measure	15 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Dose Escalation Phase STARTED	3	3	3
Dose Escalation Phase COMPLETED	3	3	3
Dose Escalation Phase NOT COMPLETED	0	0	0
Expansion Phase STARTED	11	0	43
Expansion Phase COMPLETED	11	0	43
Expansion Phase NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	15 mg Dose Lenalidomide n=14 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide n=3 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide n=46 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	Total n=63 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	8 Participants n=5 Participants	1 Participants n=7 Participants	20 Participants n=5 Participants	29 Participants n=4 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	2 Participants n=7 Participants	26 Participants n=5 Participants	34 Participants n=4 Participants
Age, Continuous	64.25 years STANDARD_DEVIATION 5.9 • n=5 Participants	63.2 years STANDARD_DEVIATION 4.95 • n=7 Participants	66.07 years STANDARD_DEVIATION 8.02 • n=5 Participants	64.51 years STANDARD_DEVIATION 6.29 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	3 Participants n=7 Participants	46 Participants n=5 Participants	63 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	3 Participants n=7 Participants	45 Participants n=5 Participants	62 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	14 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	2 Participants n=7 Participants	30 Participants n=5 Participants	43 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	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	14 Participants n=5 Participants	3 Participants n=7 Participants	46 Participants n=5 Participants	63 Participants n=4 Participants
Gleason Score ≤6	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Gleason Score 7	3 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants	15 Participants n=4 Participants
Gleason Score 8	4 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	15 Participants n=4 Participants
Gleason Score 9	4 Participants n=5 Participants	1 Participants n=7 Participants	18 Participants n=5 Participants	23 Participants n=4 Participants
Gleason Score 10	2 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	3 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	10 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	11 Participants n=5 Participants	3 Participants n=7 Participants	36 Participants n=5 Participants	50 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Location of Disease Bone only	7 Participants n=5 Participants	1 Participants n=7 Participants	16 Participants n=5 Participants	24 Participants n=4 Participants
Location of Disease Bone and lymph nodes	1 Participants n=5 Participants	2 Participants n=7 Participants	24 Participants n=5 Participants	27 Participants n=4 Participants
Location of Disease Bone and visceral (3 hepatic)	4 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Location of Disease Lymph node alone	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Location of Disease Visceral alone ( bladder and lung)	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Alkaline Phosphatase & Lactate Dehydrogenase Alkaline phosphatase	124 U/L n=5 Participants	84 U/L n=7 Participants	127 U/L n=5 Participants	125 U/L n=4 Participants
Alkaline Phosphatase & Lactate Dehydrogenase Lactate dehydrogenase	209 U/L n=5 Participants	177 U/L n=7 Participants	206.5 U/L n=5 Participants	206 U/L n=4 Participants
Prostatic Specific Antigen (PSA)	61.33 U/L n=5 Participants	61.6 U/L n=7 Participants	85.15 U/L n=5 Participants	78.7 U/L n=4 Participants
Hemoglobin	12.85 g/dL n=5 Participants	12.1 g/dL n=7 Participants	11.9 g/dL n=5 Participants	12.0 g/dL n=4 Participants

PRIMARY outcome

Timeframe: 3 weeks

Population: Data in this outcome measure is not shown per dose level because the investigator decided to pool the data for analysis since no significant difference was seen at each dose level. Outcome evaluations for cohorts of 3 and 14 patients would carry little scientific value because they are too small.

The RP2D is the dose at which there are no dose-limiting toxicities (defined as a ≥grade 3 hematological toxicity related to lenalidomide).

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=63 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Recommended Phase 2 Dose (RP2D)	25 mg	—	—

PRIMARY outcome

Timeframe: First 28 days of treatment.

DLT is defined as a ≥grade 3 non-hematological toxicity related to lenalidomide.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=63 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Count of Participants With Dose-Limiting Toxicities (DLT)	0 Participants	—	—

PRIMARY outcome

Timeframe: median time of potential follow-up of 47.5 months

TTP is evaluated from the on-study date until the date of progression or last follow-up after progression.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=63 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Median Time to Progression (TTP)	18.2 Months Interval 15.2 to 26.1	—	—

SECONDARY outcome

Timeframe: median time of potential follow-up of 47.5 months

OS is evaluated from the on-study date until the date of death or last follow-up.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=63 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Median Overall Survival of Patients Studied	24.6 Months Interval 21.7 to 31.2	—	—

SECONDARY outcome

Timeframe: After drug administration, an average of 3 months

The definition of an increase is any increase (any number greater than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. The definition of a decrease is any decrease (any number less than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=63 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration Increase in CAEC after 3 months	30 Participants	—	—
Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration decrease in CAEC after 3 months	20 Participants	—	—

SECONDARY outcome

Timeframe: median time of potential follow-up of 47.5 months

Population: This outcome measure was not done because the blood samples collected were insufficient for measuring plasma VEGF.

Serum and urine samples were collected before and after administration of Docetaxel, Prednisone, Lenalidomide and Bevacizumab to measure VEGF levels.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: median time of potential follow-up of 47.5 months

Expression of PD-1 on CD8 + T cells was evaluated by flow cytometry. High and low expression are based on the median values. Patients with a low expression of PD-1 proteins had better survival than those with a high expression.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=9 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide n=3 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide n=37 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells Low expression	21.4 Months Interval 14.2 to Not available based on small numbers.	17.8 Months Not available based on small numbers.	28.9 Months Interval 13.1 to 43.3
Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells High expression	22.4 Months Interval 18.1 to Not available based on small numbers.	26.1 Months Not available based on small numbers.	14.8 Months Interval 10.1 to 18.2

SECONDARY outcome

Timeframe: 46.5 months

Expression of TIM-3 on CD8 + T cells was evaluated by flow cytometry.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=1 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide n=1 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide n=16 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells Low expression	23.6 Months Not available based on small numbers.	NA Months Not available based on small numbers.	20.2 Months Interval 13.1 to 32.0
Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells High expression	NA Months Not available based on small numbers.	NA Months Not available based on small numbers.	12.7 Months Interval 6.7 to 27.6

SECONDARY outcome

Timeframe: median time of potential follow-up of 47.5 months

Radiologic response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is 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). Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=4 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide n=2 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide n=23 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Count of Participants With a Radiologic Response Confirmed radiologic PR	3 Participants	2 Participants	20 Participants
Count of Participants With a Radiologic Response Complete Response	0 Participants	2 Participants	0 Participants
Count of Participants With a Radiologic Response Stable Disease	1 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: median time of potential follow-up of 47.5 months

PSA decline is defined as a ≥50% decline in measurable disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm by chest x-ray, as ≥10 mm with computed tomography, or ≥10 mm with calipers by clinical exam.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=13 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide n=3 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide n=45 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Count of Participants With Prostatic Antigen-Specific (PSA) Declines Participants with PSA>30%	13 Participants	3 Participants	41 Participants
Count of Participants With Prostatic Antigen-Specific (PSA) Declines Participants with PSA>50%	12 Participants	3 Participants	40 Participants
Count of Participants With Prostatic Antigen-Specific (PSA) Declines Participants with PSA>90%	5 Participants	1 Participants	27 Participants
Count of Participants With Prostatic Antigen-Specific (PSA) Declines Not Evaluable	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 93 months and 22 days.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Single Arm - 4 Drug Combination n=14 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 Docetaxel: 75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	20 mg Dose Lenalidomide n=3 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day	25 mg Dose Lenalidomide n=46 Participants A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalation approach in combination with docetaxel, Bevacizumab and prednisone. Bevacizumab: 15 mg/kg cycle 1 day 1, repeated every 21 days Lenalidomide: Once daily days 1-14 of every 21 days Docetaxel: 75 mg/m(2) intravenous (IV) over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle) Prednisone: 10 mg orally every day
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination	14 Participants	3 Participants	46 Participants

Adverse Events

15 mg Dose Lenalidomide

Serious events: 13 serious events

Other events: 14 other events

Deaths: 1 deaths

20 mg Dose Lenalidomide

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

25 mg Dose Lenalidomide

Serious events: 45 serious events

Other events: 46 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Ravi Madan

National Cancer Institute

Phone: 301-480-7168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place