Immunotherapy With APC8015 (Sipuleucel-T, Provenge) for Asymptomatic, Metastatic, Hormone-Refractory Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01133704

Recruitment Status : Completed

First Posted : May 31, 2010

Results First Posted : September 2, 2010

Last Update Posted : September 8, 2010

Sponsor:

Information provided by:

Dendreon

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Hormone-Refractory Prostate Cancer
Interventions	Biological: sipuleucel-T Biological: APC-Placebo
Enrollment	98

Participant Flow

Recruitment Details	Participants were randomized between May 2000 and March 2003 across 24 clinical trial sites.
Pre-assignment Details	Participants were screened for evaluation of subject eligibility and performance of baseline tests/procedures.


Arm/Group Title	Sipuleucel-T (APC8015)	Placebo
Arm/Group Description	All subjects randomized to receive ...	All subjects randomized to receive ...
Arm/Group Description	All subjects randomized to receive sipuleucel-T. Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.	All subjects randomized to receive placebo. Approximately one-third of the autologous quiescent APCs prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.
Period Title: Overall Study
Started	65	33
Completed	16 ^[1]	7 ^[1]
Not Completed	49	26
Reason Not Completed
Death	44	26
Patient refused to continue	4	0
Study Closure	1	0
[1] (including 3 year follow-up)

Baseline Characteristics

Arm/Group Title		Sipuleucel-T (APC8015)	Placebo	Total
Arm/Group Description		All subjects randomized to receive ...	All subjects randomized to receive ...	Total of all reporting groups
Arm/Group Description		All subjects randomized to receive sipuleucel-T. Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.	All subjects randomized to receive placebo. Approximately one-third of the autologous quiescent APCs prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.	Total of all reporting groups
Overall Number of Baseline Participants		65	33	98
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	65 participants	33 participants	98 participants
		69.6 (8.2)	70.6 (7.8)	69.9 (8.1)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	65 participants	33 participants	98 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	65 100.0%	33 100.0%	98 100.0%

Outcome Measures

1.Primary Outcome


Title	Overall Time to Disease Progression
Description	Overall time to disease progression in subjects with asymptomatic
Description	Overall time to disease progression in subjects with asymptomatic metastatic hormone-refractory prostate cancer treated with sipuleucel-T (APC8015) compared to overall time to disease progression in subjects treated with placebo.
Time Frame	from randomization to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Sipuleucel-T (APC8015)	Placebo
Arm/Group Description:	All subjects randomized to receive ...	All subjects randomized to receive ...
Arm/Group Description:	All subjects randomized to receive sipuleucel-T. Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.	All subjects randomized to receive placebo. Approximately one-third of the autologous quiescent APCs prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.
Overall Number of Participants Analyzed	65	33
Median (95% Confidence Interval) Unit of Measure: Weeks
	10.9 (9.3 to 17.7)	9.9 (8.4 to 18.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sipuleucel-T (APC8015), Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.719
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95% 0.69 to 1.70
	Estimation Comments	Obtained from a Cox proportional hazards model with treatment group as the independent variable, stratified by bisphosphonate use (placebo/sipuleucel-T)

2.Secondary Outcome


Title	Overall Survival
Description	Subjects were followed for 3 years from the time of randomization or u...
Description	Subjects were followed for 3 years from the time of randomization or until death.
Time Frame	Time from randomization until 36 months

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Sipuleucel-T (APC8015)	Placebo
Arm/Group Description:	All subjects randomized to receive ...	All subjects randomized to receive ...
Arm/Group Description:	All subjects randomized to receive sipuleucel-T. Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.	All subjects randomized to receive placebo. Approximately one-third of the autologous quiescent APCs prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.
Overall Number of Participants Analyzed	65	33
Median (95% Confidence Interval) Unit of Measure: Months
	19.0 (13.6 to 31.9)	15.7 (12.8 to 25.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sipuleucel-T (APC8015), Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.331
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95% 0.78 to 2.07
	Estimation Comments	Obtained from a Cox proportional hazards model with treatment as the independent variable, and stratified by bisphosphonate use (placebo/sipuleucel-T).

Adverse Events

Time Frame	From randomization through 36 months. Median follow-up was 36 months.
Adverse Event Reporting Description	Safety population: All subjects randomized to each arm who underwent at least one leukapheresis procedure. Not all randomized subjects underwent at least one leukapheresis procedure.

Arm/Group Title	Sipuleucel-T (APC8015)	Placebo
Arm/Group Description	All subjects randomized to receive ...	All subjects randomized to receive ...
Arm/Group Description	All subjects randomized to receive sipuleucel-T. Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.	All subjects randomized to receive placebo. Approximately one-third of the autologous quiescent APCs prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.
All-Cause Mortality
	Sipuleucel-T (APC8015)	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Sipuleucel-T (APC8015)	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	13/65 (20.00%)	9/31 (29.03%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/65 (1.54%)	1/31 (3.23%)
Disseminated intravascular coagulation ^† 1	1/65 (1.54%)	0/31 (0.00%)
Cardiac disorders
Atrial flutter ^† 1	1/65 (1.54%)	0/31 (0.00%)
Cardiac failure ^† 1	1/65 (1.54%)	0/31 (0.00%)
Cardiac failure congestive ^† 1	0/65 (0.00%)	1/31 (3.23%)
Supraventricular tachycardia ^† 1	0/65 (0.00%)	1/31 (3.23%)
Tachycardia ^† 1	1/65 (1.54%)	0/31 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	0/65 (0.00%)	1/31 (3.23%)
Intestinal obstruction ^† 1	0/65 (0.00%)	1/31 (3.23%)
Nausea ^† 1	1/65 (1.54%)	0/31 (0.00%)
General disorders
Adverse drug reaction ^† 1	1/65 (1.54%)	0/31 (0.00%)
Chills ^† 1	3/65 (4.62%)	0/31 (0.00%)
Disease Progression ^† 1	1/65 (1.54%)	0/31 (0.00%)
Pain ^† 1	1/65 (1.54%)	0/31 (0.00%)
Pyrexia ^† 1	2/65 (3.08%)	0/31 (0.00%)
Infections and infestations
Bacteraemia ^† 1	1/65 (1.54%)	0/31 (0.00%)
Bacterial sepsis ^† 1	1/65 (1.54%)	0/31 (0.00%)
Catheter sepsis ^† 1	1/65 (1.54%)	0/31 (0.00%)
Cellulitis ^† 1	0/65 (0.00%)	1/31 (3.23%)
Extradural abscess ^† 1	1/65 (1.54%)	0/31 (0.00%)
Sepsis ^† 1	1/65 (1.54%)	1/31 (3.23%)
Staphylococcal bacteraemia ^† 1	1/65 (1.54%)	0/31 (0.00%)
Staphylococcal sepsis ^† 1	1/65 (1.54%)	0/31 (0.00%)
Urinary tract infection ^† 1	1/65 (1.54%)	0/31 (0.00%)
Metabolism and nutrition disorders
Dehydration ^† 1	2/65 (3.08%)	1/31 (3.23%)
Hyperglycaemia ^† 1	0/65 (0.00%)	1/31 (3.23%)
Musculoskeletal and connective tissue disorders
Back Pain ^† 1	1/65 (1.54%)	1/31 (3.23%)
Chest wall pain ^† 1	1/65 (1.54%)	0/31 (0.00%)
Pathological fracture ^† 1	0/65 (0.00%)	1/31 (3.23%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine ^† 1	1/65 (1.54%)	0/31 (0.00%)
Skin cancer ^† 1	0/65 (0.00%)	1/31 (3.23%)
Small cell lung cancer stage unspecified ^† 1	0/65 (0.00%)	1/31 (3.23%)
Nervous system disorders
Brain mass ^† 1	1/65 (1.54%)	0/31 (0.00%)
Cerebral haemorrhage ^† 1	1/65 (1.54%)	0/31 (0.00%)
Cerebrovascular accident ^† 1	1/65 (1.54%)	0/31 (0.00%)
Facial palsy ^† 1	1/65 (1.54%)	0/31 (0.00%)
Headache ^† 1	1/65 (1.54%)	0/31 (0.00%)
Lacunar infarction ^† 1	1/65 (1.54%)	0/31 (0.00%)
Paraesthesia ^† 1	1/65 (1.54%)	0/31 (0.00%)
Renal and urinary disorders
Haematuria ^† 1	1/65 (1.54%)	0/31 (0.00%)
Urinary retention ^† 1	0/65 (0.00%)	1/31 (3.23%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/65 (1.54%)	0/31 (0.00%)
Pulmonary embolism ^† 1	0/65 (0.00%)	1/31 (3.23%)
Vascular disorders
Deep vein thrombosis ^† 1	0/65 (0.00%)	2/31 (6.45%)
Embolism ^† 1	0/65 (0.00%)	1/31 (3.23%)
Hypertension ^† 1	2/65 (3.08%)	0/31 (0.00%)
Hypotension ^† 1	0/65 (0.00%)	1/31 (3.23%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (11.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sipuleucel-T (APC8015)	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	63/65 (96.92%)	29/31 (93.55%)
Blood and lymphatic system disorders
Anaemia ^† 1	13/65 (20.00%)	1/31 (3.23%)
Gastrointestinal disorders
Constipation ^† 1	5/65 (7.69%)	4/31 (12.90%)
Diarrhoea ^† 1	4/65 (6.15%)	2/31 (6.45%)
Dyspepsia ^† 1	1/65 (1.54%)	2/31 (6.45%)
Hypoaesthesia Oral ^† 1	4/65 (6.15%)	1/31 (3.23%)
Nausea ^† 1	9/65 (13.85%)	1/31 (3.23%)
Vomiting ^† 1	6/65 (9.23%)	1/31 (3.23%)
General disorders
Asthenia ^† 1	12/65 (18.46%)	2/31 (6.45%)
Chills ^† 1	34/65 (52.31%)	2/31 (6.45%)
Fatigue ^† 1	27/65 (41.54%)	5/31 (16.13%)
Influenza Like Illness ^† 1	4/65 (6.15%)	2/31 (6.45%)
Malaise ^† 1	4/65 (6.15%)	0/31 (0.00%)
Oedema Peripheral ^† 1	7/65 (10.77%)	5/31 (16.13%)
Pain ^† 1	9/65 (13.85%)	2/31 (6.45%)
Pyrexia ^† 1	19/65 (29.23%)	3/31 (9.68%)
Injury, poisoning and procedural complications
Citrate Toxicity ^† 1	10/65 (15.38%)	5/31 (16.13%)
Metabolism and nutrition disorders
Anorexia ^† 1	6/65 (9.23%)	1/31 (3.23%)
Dehydration ^† 1	4/65 (6.15%)	1/31 (3.23%)
Hyperglycemia ^† 1	0/65 (0.00%)	2/31 (6.45%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	10/65 (15.38%)	9/31 (29.03%)
Back Pain ^† 1	14/65 (21.54%)	8/31 (25.81%)
Bone Pain ^† 1	0/65 (0.00%)	2/31 (6.45%)
Chest Wall Pain ^† 1	7/65 (10.77%)	1/31 (3.23%)
Groin Pain ^† 1	0/65 (0.00%)	2/31 (6.45%)
Myalgia ^† 1	5/65 (7.69%)	2/31 (6.45%)
Neck Pain ^† 1	2/65 (3.08%)	2/31 (6.45%)
Pain in Extremity ^† 1	7/65 (10.77%)	7/31 (22.58%)
Shoulder Pain ^† 1	3/65 (4.62%)	3/31 (9.68%)
Nervous system disorders
Dizziness ^† 1	8/65 (12.31%)	2/31 (6.45%)
Headache ^† 1	14/65 (21.54%)	3/31 (9.68%)
Lethargy ^† 1	0/65 (0.00%)	2/31 (6.45%)
Paraesthesia ^† 1	6/65 (9.23%)	5/31 (16.13%)
Paraesthesia Oral ^† 1	5/65 (7.69%)	3/31 (9.68%)
Tremor ^† 1	5/65 (7.69%)	0/31 (0.00%)
Psychiatric disorders
Insomnia ^† 1	1/65 (1.54%)	4/31 (12.90%)
Renal and urinary disorders
Urinary Retention ^† 1	3/65 (4.62%)	2/31 (6.45%)
Reproductive system and breast disorders
Gynaecomastia ^† 1	2/65 (3.08%)	2/31 (6.45%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	4/65 (6.15%)	1/31 (3.23%)
Dyspnoea Exertional ^† 1	3/65 (4.62%)	2/31 (6.45%)
Vascular disorders
Deep Vein Thrombosis ^† 1	0/65 (0.00%)	2/31 (6.45%)
Hypertension ^† 1	5/65 (7.69%)	0/31 (0.00%)
Pallor ^† 1	7/65 (10.77%)	3/31 (9.68%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (11.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

A provision provides for sponsor review up to 45 days with the right to request modification based on disclosure of confidential information; extendable by 60 days to file a patent application.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Kathleen Picha
Organization:	Dendreon Corporation
Phone:	206-265-4545
EMail:	kpicha@dendreon.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Small EJ, Higano CS, Kantoff PW, Whitmore JB, Frohlich MW, Petrylak DP. Time to disease-related pain and first opioid use in patients with metastatic castration-resistant prostate cancer treated with sipuleucel-T. Prostate Cancer Prostatic Dis. 2014 Sep;17(3):259-64. doi: 10.1038/pcan.2014.21. Epub 2014 Jun 24.

Layout table for additonal information

ClinicalTrials.gov Identifier:	NCT01133704
Other Study ID Numbers:	D9902A
First Submitted:	May 27, 2010
First Posted:	May 31, 2010
Results First Submitted:	June 1, 2010
Results First Posted:	September 2, 2010
Last Update Posted:	September 8, 2010

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