Trial Outcomes & Findings for Study to Evaluate Safety and Effectiveness of Lenalidomide in Combination With Docetaxel and Prednisone for Patients With Castrate-Resistant Prostate Cancer (NCT NCT00988208)

Last Updated: 2018-04-04

Results Overview

Overall survival (OS) was the time from the date of randomization to the date of death from any cause. If no death was reported for a participant before the cut-off date for OS analysis, OS was censored at the last date at which the participant was alive. The median OS was calculated based on Kaplan-Meier estimates and corresponding 95% confidence interval (CI) was calculated using the method provided by Brookmeyer and Crowley.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1059 participants

Primary outcome timeframe

From randomization until death from any cause up to the cut-off date of 13 January 2012; up to approximately 26 months

Results posted on

2018-04-04

Participant Flow

Following a safety and efficacy data review by the Data Monitoring Committee( DMC), the trial was stopped for futility. At that time, 1059 participants had been randomized and 1046 treated with either lenalidomide plus docetaxel and prednisone or placebo plus docetaxel and prednisone. A data cutoff date of 13 January 2012 was established.

Participants who had started a treatment cycle at the time of termination request were allowed to complete the cycle and have their discontinuation visit at the next cycle (21 days later). The safety follow-up of 28 days was also added to ensure all adverse events were followed.

Participant milestones

Participant milestones
Measure	Docetaxel/Prednisone/Placebo (DP) Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Overall Study STARTED	526	533
Overall Study Treated	521	525
Overall Study COMPLETED	95	95
Overall Study NOT COMPLETED	431	438

Reasons for withdrawal

Reasons for withdrawal
Measure	Docetaxel/Prednisone/Placebo (DP) Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Overall Study Adverse Event	71	122
Overall Study Disease Progression	103	89
Overall Study Withdrawal by Subject	50	57
Overall Study Death	9	15
Overall Study Lost to Follow-up	2	3
Overall Study Protocol Violation	9	2
Overall Study Sponsor Decision	102	78
Overall Study Clinical Progression	17	16
Overall Study Biochemical Progression	21	7
Overall Study Clinical Deterioration	7	14
Overall Study Subject Decision/Investigator Discretion	32	32
Overall Study Other	8	3

Baseline Characteristics

Study to Evaluate Safety and Effectiveness of Lenalidomide in Combination With Docetaxel and Prednisone for Patients With Castrate-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docetaxel/Prednisone/Placebo (DP) n=526 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=533 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Total n=1059 Participants Total of all reporting groups
Baseline PSA (Prostate Specific Antigen) Levels	290.359 (ng/ml) STANDARD_DEVIATION 659.1583 • n=5 Participants	316.501 (ng/ml) STANDARD_DEVIATION 776.1133 • n=7 Participants	303.542 (ng/ml) STANDARD_DEVIATION 720.2895 • n=5 Participants
Metastatic Sites of Disease Outside of Prostate Bone only	157 Participants n=5 Participants	169 Participants n=7 Participants	326 Participants n=5 Participants
Metastatic Sites of Disease Outside of Prostate Soft tissues only	94 Participants n=5 Participants	104 Participants n=7 Participants	198 Participants n=5 Participants
Metastatic Sites of Disease Outside of Prostate Both bone and Soft tissues	273 Participants n=5 Participants	259 Participants n=7 Participants	532 Participants n=5 Participants
Metastatic Sites of Disease Outside of Prostate None	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	68.4 years STANDARD_DEVIATION 7.79 • n=5 Participants	68.9 years STANDARD_DEVIATION 7.98 • n=7 Participants	68.7 years STANDARD_DEVIATION 7.89 • n=5 Participants
Age, Customized <65 years	171 Participants n=5 Participants	163 Participants n=7 Participants	334 Participants n=5 Participants
Age, Customized > = to 65 years and < = 75years	246 Participants n=5 Participants	244 Participants n=7 Participants	490 Participants n=5 Participants
Age, Customized >75 years	109 Participants n=5 Participants	126 Participants n=7 Participants	235 Participants n=5 Participants
Sex/Gender, Customized male	526 Participants n=5 Participants	533 Participants n=7 Participants	1059 Participants n=5 Participants
Sex/Gender, Customized female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment US or Canada	136 Participants n=5 Participants	140 Participants n=7 Participants	276 Participants n=5 Participants
Region of Enrollment EU or Australia	329 Participants n=5 Participants	330 Participants n=7 Participants	659 Participants n=5 Participants
Region of Enrollment Rest of World (Includes 4 additional countries)	61 Participants n=5 Participants	63 Participants n=7 Participants	124 Participants n=5 Participants
Race, Customized White	433 Participants n=5 Participants	436 Participants n=7 Participants	869 Participants n=5 Participants
Race, Customized Other or no answer	55 Participants n=5 Participants	67 Participants n=7 Participants	122 Participants n=5 Participants
Race, Customized Black or African American	25 Participants n=5 Participants	21 Participants n=7 Participants	46 Participants n=5 Participants
Race, Customized Asian	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race, Customized American Indian or Alaska Native	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Weight	86.4 kilograms STANDARD_DEVIATION 16.18 • n=5 Participants	86 kilograms STANDARD_DEVIATION 15.70 • n=7 Participants	86.2 kilograms STANDARD_DEVIATION 15.93 • n=5 Participants
Height	174.0 centimeters STANDARD_DEVIATION 7.81 • n=5 Participants	174.4 centimeters STANDARD_DEVIATION 7.38 • n=7 Participants	174.2 centimeters STANDARD_DEVIATION 7.60 • n=5 Participants
Body Mass Index	28.6 kg/m^2 STANDARD_DEVIATION 5.02 • n=5 Participants	28.3 kg/m^2 STANDARD_DEVIATION 4.60 • n=7 Participants	28.4 kg/m^2 STANDARD_DEVIATION 4.81 • n=5 Participants
Body Mass Index, Categorical <25 kg/m^2	134 Participants n=5 Participants	138 Participants n=7 Participants	272 Participants n=5 Participants
Body Mass Index, Categorical 25-30 kg/m^2	221 Participants n=5 Participants	243 Participants n=7 Participants	464 Participants n=5 Participants
Body Mass Index, Categorical >30 kg/m^2	171 Participants n=5 Participants	152 Participants n=7 Participants	323 Participants n=5 Participants
ECOG Performance Status 0 (Fully Active)	257 Participants n=5 Participants	252 Participants n=7 Participants	509 Participants n=5 Participants
ECOG Performance Status 1 (Restrictive but ambulatory)	247 Participants n=5 Participants	256 Participants n=7 Participants	503 Participants n=5 Participants
ECOG Performance Status 2 (Ambulatory but unable to work)	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
ECOG Performance Status 3 (Limited self-care)	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
ECOG Performance Status Not specified	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Type of Disease Progression Rising PSA only	146 Participants n=5 Participants	159 Participants n=7 Participants	305 Participants n=5 Participants
Type of Disease Progression Radiographic progression	380 Participants n=5 Participants	374 Participants n=7 Participants	754 Participants n=5 Participants
Prior Radiotherapy Yes	308 Participants n=5 Participants	312 Participants n=7 Participants	620 Participants n=5 Participants
Prior Radiotherapy No	218 Participants n=5 Participants	221 Participants n=7 Participants	439 Participants n=5 Participants
Prior Cancer Surgery Yes	335 Participants n=5 Participants	358 Participants n=7 Participants	693 Participants n=5 Participants
Prior Cancer Surgery No	191 Participants n=5 Participants	175 Participants n=7 Participants	366 Participants n=5 Participants
Other Prior Anti-Cancer Therapy Yes	79 Participants n=5 Participants	71 Participants n=7 Participants	150 Participants n=5 Participants
Other Prior Anti-Cancer Therapy No	447 Participants n=5 Participants	462 Participants n=7 Participants	909 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until death from any cause up to the cut-off date of 13 January 2012; up to approximately 26 months

Population: Intent-to-Treat (ITT) population defined as all randomized patients irrespective of whether they received treatment or not.

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=526 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=533 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Overall Survival (OS)	NA weeks Interval 75.71 to Median overall survival was not reached for the DP arm as only 92 (17.5 %) of participants had died at the time of the data cut off.	77 weeks Interval 64.29 to 81.71

SECONDARY outcome

Timeframe: From randomization until disease progression or death from any cause; up to the cut-off date of 13 Jan 2012; maximum time on study was approximately 26 months

Population: Based on the Intent to treat population (ITT), defined as all randomized patients irrespective of whether they received treatment or not.

PFS was the time from randomization to disease progression, or death, whatever occurred first. Progression criteria was met by analysis of target and non-target lesions as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters while on study or the appearance of one or more new lesions; an increase of at least 5mm as a total sum. Lymph nodes identified as target lesions (≥ 15 mm diameter in short axis) will be followed and reported by changes in diameter of short axis; or the unequivocal progression of a non-target lesion defined as an increase in the overall disease burden based on the change in non-measurable disease that is comparable in scope to the increase required to declare PD for measurable disease; Two or more new bone lesions as detected by bone scan

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=526 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=533 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Progression-Free Survival (PFS)	46 Weeks Interval 42.14 to 53.57	45 Weeks Interval 38.0 to 46.14

SECONDARY outcome

Timeframe: From day 1 to data cut-off 13 January 2012; maximum time on study was approximately 26 months

Population: Based on the ITT population

Objective response (OR) is defined as having complete response (CR) or partial response (PR) as best overall response based on RECIST Criteria 1.1 and defines a CR = Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to \<10mm; PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions taking as a reference the smallest sum of diameters and an absolute increase of ≥5 mm; the appearance of ≥1 new lesions; Stable Disease (SD)= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size \<10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=526 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=533 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Percentage of Participants With an Objective Response According to Response Evaluation Criteria in Solid Tumors - RECIST Version 1.1 Criteria	24.3 percentage of participants	22.1 percentage of participants

SECONDARY outcome

Timeframe: From the time from of first dose of study drug administration to 28 days after the last dose of study drug and up to the data cut off date of 13 January 2012; the maximum duration of study drug was 93 weeks for DP and 90.6 weeks for DPL

Population: The Safety Population is defined as all randomized participants who receive at least one dose of the study treatment (lenalidomide/placebo, Docetaxel, or Prednisone).

A TEAE is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal;

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=521 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=525 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Number of Participants With Treatment Emergent Adverse Events (AEs) Any SAE related to lenalidomide or placebo	62 participants	167 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any TEAE	512 participants	517 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any TEAE related to lenalidomide or placebo	379 participants	412 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any TEAE related to docetaxel/prednisone	475 participants	481 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any severity grade 3-4 TEAE	303 participants	381 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any serious AE (SAE)	171 participants	279 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any SAE related to docetaxel/prednisone	86 participants	182 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE causing discontinuation of lenalidomide/PBO	82 participants	150 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE causing withdrawal of docetaxel/prednisone	127 participants	169 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any TEAE leading to death	16 participants	24 participants

SECONDARY outcome

Timeframe: The date when the first consent form was signed to the last date of AE data collection;up to 5 years; up to the date of the final data analysis date of 20 April 2017

Population: The Safety Population is defined as all randomized participants who receive at least one dose of the study treatment (lenalidomide/placebo, Docetaxel, or Prednisone).

Percentage of Participants Who Received Post-Study Therapies for advanced Prostate Cancer.

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=521 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=525 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Percentage of Participants Who Received Post-Study Therapies	70.8 Percentage of Participants	69.0 Percentage of Participants

SECONDARY outcome

Timeframe: The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days

Population: The Safety Population is defined as all randomized participants who receive at least one dose of the study treatment lenalidomide/placebo, Docetaxel, or Prednisone).

Second primary malignancies were monitored as events of interest and reported as serious adverse events throughout the course of the trial.

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=521 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=525 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial Invasive Secondary Primary Malignancies	1.3 percentage of participants	1.7 percentage of participants
Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial Non-invasive Secondary Primary Malignancies	0.4 percentage of participants	1.0 percentage of participants

SECONDARY outcome

Timeframe: The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days

Population: The Safety Population is defined as all randomized participants who receive at least one dose of the study treatment (lenalidomide/placebo, Docetaxel, or Prednisone).

Time of Onset of Secondary Primary Malignancies was considered an event of interest

Outcome measures

Outcome measures
Measure	Docetaxel/Prednisone/Placebo (DP) n=521 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and identically matching placebo capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.	Docetaxel/Prednisone/Lenalidomide (DPL) n=525 Participants Participants received docetaxel 75 mg/m\^2 by intravenous (IV) administration over 60 minutes on Day 1, prednisone 5 mg orally twice a day (BID) and lenalidomide 25 mg capsules daily (QD) on Days 1-14 in each 21-day treatment cycle.
Time to Onset of Secondary Primary Malignancies	29.7 months Interval 0.6 to 48.7	19.7 months Interval 3.7 to 65.0

Adverse Events

Docetaxel/Prednisone/Lenalidomide (DPL)

Serious events: 283 serious events

Other events: 513 other events

Deaths: 0 deaths

Docetaxel/ Prednisone/and Placebo (DP)

Serious events: 176 serious events

Other events: 511 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Manager , Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Multicenter publication must include input from investigators and Celgene, agreement to be established before publication. It has priority over subset (single center) publication, for duration of 24 months after study completion. Individual investigators have publication rights after multicenter publication is complete (or 24 months after study completion), whichever is first. In this case, Celgene has the right to comment and right to ask delay of publication for 60 days.
Publication restrictions are in place

Restriction type: OTHER