Concurrent vs. Sequential Sipuleucel-T & Abiraterone Treatment in Men With Metastatic Castrate Resistant Prostate Cancer

• Sponsor: Dendreon (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01487863
• Collaborator: (none)
• Enrollment: 69
• Locations: 21
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the impact of concurrent versus sequential administration of abiraterone acetate plus prednisone on the ability to manufacture sipuleucel-T (by assessing sipuleucel-T product parameters), and to assess the safety and efficacy of sipuleucel-T with concurrent or sequential administration of abiraterone acetate plus prednisone in men with metastatic castrate resistant prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Metastatic; Hormone Refractory Prostate Cancer; Castration-resistant Prostate Cancer	Biological: sipuleucel-T; Drug: abiraterone acetate	Phase 2

Detailed Description

Subjects underwent screening procedures at the Screening Visit to ensure that they met the inclusion and exclusion criteria outlined in the protocol. Subjects were evaluated for eligibility criteria, and if eligible, were registered and randomized in a 1:1 into either the Concurrent Arm or the Sequential Arm.

Subjects in both arms underwent a standard 1.5 to 2.0 blood volume leukapheresis, followed approximately 3 days later by an intravenous (IV) infusion of sipuleucel-T. This process occurred at approximately 2-week intervals. A course of sipuleucel-T treatment comprised three infusions.

Following the first infusion, subjects were limited to a maximum of three total product failures for all subsequent infusions, due specifically to insufficient total nucleated cell (TNC) count and/or CD54 upregulation. These subjects received no further leukaphereses or sipuleucel-T infusions, but did receive abiraterone acetate plus prednisone per the schedule of the arm to which they were randomized. All subjects received a total of 26 weeks of abiraterone acetate plus prednisone therapy.

All immune monitoring (IM) endpoints were collected from all subjects who received at least one infusion. Cellular and serological immune responses were assessed for subjects in both arms. In both arms, IM blood samples were collected at baseline (screening); pre-leukapheresis 2 and 3; post-infusion 1, 2, and 3; and weeks 6, 10, 14, and 26, with the timing of IM visits based on the onset of treatment (Day 0). Day 0 was the day of the first infusion. Post-infusion blood draws occurred at 3 hours (allowable window 1-24 hours) after each infusion. If a subject received only one or two infusions, immune samples were still drawn at the scheduled time points based on the first infusion (Day 0). If the subject was not scheduled to undergo further leukapheresis, no other pre-leukapheresis procedures were conducted.

During the active follow-up phase, subjects were followed from registration through the Post-Treatment Visit (30-37 days post-last study treatment), or until disease progression, unacceptable toxicity, or death, whichever occurred first.

During the long-term follow-up (LTFU) phase, subjects were followed from the Post-Treatment Visit for up to 3 years from the date of registration/randomization. During the LTFU phase, only new treatment-related serious adverse event (SAE)s, cerebrovascular event (CVE)s (regardless of causality), the first anti-cancer therapy and first chemotherapy, and survival status were collected via a quarterly telephone call.

Overall survival was measured as the time from randomization until death over a 3-year period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Open-label, Phase 2 Trial of Sipuleucel-T With Concurrent Versus Sequential Administration of Abiraterone Acetate Plus Prednisone in Men With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Concurrent Arm Subjects received sipuleucel-T concurrent with abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone treatment started the next day after the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death, occurred.	Biological: sipuleucel-T; Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).; Other Names: PROVENGE(R) APC8015 ; Drug: abiraterone acetate; Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.; Other Names: ZYTIGA(R)
Experimental: Sequential Arm Subjects received sipuleucel-T therapy followed by abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone started at week 10 from the start of the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death, occurred.	Biological: sipuleucel-T; Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).; Other Names: PROVENGE(R) APC8015 ; Drug: abiraterone acetate; Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.; Other Names: ZYTIGA(R)

Outcome Measures

Primary Outcome Measures

1. Cumulative CD54 Upregulation Ratio Between the Cohorts. [Over the course of sipuleucel-T therapy (approximately 1 month)]

   An analysis of variance model for the log transformed cumulative CD54 upregulation ratio (CD54 upregulation is the fold increase in the final product (FP) from buoyant density separations (BDS) step 65. BDS65 step refers to sample taken after both BDS77 and BDS65 but before ex vivo culture in the presence of antigen PA2024. FP refers to sample taken after ex vivo culture) that includes the antigen concentration cohort as the independent variable was performed. Subjects who received all 3 infusions were included.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• histologically documented prostate cancer confirmed by a pathology report from prostate biopsy or radical prostatectomy specimen

• metastatic status as evidenced by imaging obtained </= 56 days prior to registration demonstrating bone metastasis or lymph node metastasis

• castrate resistant prostate cancer: castrate levels of testosterone (</= 50 ng/dL); evidence of disease progression concomitant with surgical or medical castration

• serum PSA >/= 2.0 ng/mL

• castrate levels of testosterone (</= 50 ng/dL) achieved via medical or surgical castration

• baseline Eastern Cooperative Oncology Group (ECOG) performance status of </= 1

• systolic blood pressure (BP) </= 140 mm Hg and diastolic BP </= 90 mm Hg at screening

• adequate baseline hematologic, renal, and liver functions

• must live in a permanent residence within a comfortable driving distance (round trip within one day) of the clinical trial site

Exclusion Criteria:

• the presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites

• New York Heart Association Class III or IV heart failure

• any medical condition that may be compromised by increases in blood pressure, hypokalemia, or fluid retention

• Child-Pugh Class B or C hepatic insufficiency

• spinal cord compression, imminent long bone fracture, or any other condition likely to require radiation therapy and/or steroids for pain control

• known adrenalcortical insufficiency

• any medical contraindications to receiving prednisone

• prior treatment with sipuleucel-T

• previous treatment with abiraterone acetate (Zytiga(R)) or ipilimumab (Yervoy(TM))

• a requirement for systemic immunosuppressive therapy for any reason. Use of inhaled, intra-nasal, intra-articular, and topical steroids was allowed.

• treatment with any investigational vaccine or immunotherapy

• treatment with any chemotherapy prior to registration.

• a history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease-free at the time of registration. Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years at the time of registration.

• myocardial infarction or ventricular or atrial arrhythmia within 6 months prior to registration

• ongoing anti-androgen withdrawal response.

• systemic steroid use within ≤ 60 days of registration

• treatment with denosumab (Xgeva(R) or Prolia (R)) within ≤ 3 months prior to registration

• positive test for human immunodeficiency virus (HIV) or human T cell lymphotrophic virus (HTLV) infections. Subjects with a positive test for hepatitis B or hepatitis C were allowed provided they meet the liver function test (LFT) criteria and have no signs of acute infection or active disease.

• treatment with any of the following medications or interventions within 28 days prior to registration: external beam radiation or major surgery requiring general anesthetic; saw palmetto; megestrol acetate (Megace(R)), diethylstilbestrol, and cyproterone; 5-alpha-reductase inhibitors (e.g. finasteride [Proscar(R)], dutasteride [Avodart(R)]); steroidal anti-androgen therapy; any other systemic therapy for prostate cancer, except for medical castration; treatment with any other investigational product for prostate cancer; substrates of CYP2D6 (e.g. including but not limited to thioridazine); inhibitors of CYP3A4 (e.g. including but not limited to ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, and voriconazole); inducers of CYP3A4 (e.g. including but not limited to phenytoin, carbamazepine, rifampin, rifapentine, and phenobarbital)

• a requirement for treatment with opioid analgesics within 21 days prior to registration

• an active infection or infection requiring parenteral antibiotic therapy or causing fever within 7 days of registration

• any medical intervention, or other condition, or any other circumstance that, in the opinion of the Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Medical Center - La Jolla	La Jolla	California	United States	92037
2	Moores UCSD Cancer Center	La Jolla	California	United States	92093
3	Cancer Center Oncology Medical Group	La Mesa	California	United States	91942
4	UCSD Medical Center - Hillcrest	San Diego	California	United States	92103
5	Medical Oncology Associates - SD	San Diego	California	United States	92123
6	Sharp Rees-Stealy	San Diego	California	United States	92123
7	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
8	The Urology Center of Colorado	Denver	Colorado	United States	80211
9	Georgetown University Medical Center - Lombardi Cancer Center	Washington	District of Columbia	United States	20007
10	Indiana University	Indianapolis	Indiana	United States	46202
11	Mid Atlantic Urology Associates, Mid Atlantic Clinical Research	Greenbelt	Maryland	United States	20770
12	GU Research Center, LLC	Omaha	Nebraska	United States	68130
13	NYU Clinical Cancer Center, NYU Langone Medical Center	New York	New York	United States	10016
14	The Mount Sinai Medical Center	New York	New York	United States	10029
15	Associated Medical Professionals of NY, PLLC	Oneida	New York	United States	13421
16	Associated Medical Professionals of New York, PLLC	Syracuse	New York	United States	13210
17	Providence Cancer Center Oncology and Hematology Care	Portland	Oregon	United States	97213
18	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
19	Urology Associates, P.C.	Nashville	Tennessee	United States	37209
20	Urology of Virginia	Virginia Beach	Virginia	United States	23462
21	Virginia Mason Medical Center	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Dendreon

Investigators

• Study Director: Robert Israel, MD, Valeant Pharmaceuticals North America LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dendreon
• ClinicalTrials.gov Identifier: NCT01487863
• Other Study ID Numbers: P11-3
• First Posted: Dec 8, 2011
• Last Update Posted: Mar 19, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Dendreon: prostate cancer; prostate; androgen independent prostate cancer (AIPC); androgen-independent; androgen independent; hormone insensitive; hormone-insensitive; prostate specific antigen (PSA); prostatic adenocarcinoma; hormone-refractory; hormone refractory; hormone refractory prostate cancer (HRPC); immune therapy; immunotherapy; vaccine; dendritic cells; antigen-presenting cells; antigen presenting cells; cancer vaccine; therapeutic vaccine; therapeutic cancer vaccine; recombinant; biological; biopharmaceutical; biotechnology; biotech; castration resistant prostate cancer (CRPC); castration-resistant prostate cancer (CRPC); castration-resistance; sipuleucel-T; abiraterone; prednisone; sequence; sequencing
• Additional relevant MeSH terms: Prostatic Neoplasms; Abiraterone Acetate

Study Results

Participant Flow

Arm/Group Title	Concurrent Arm	Sequential Arm
Arm/Group Description	Subjects received sipuleucel-T with concurrent abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone treatment started the next day after the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.	Subjects received sipuleucel-T therapy followed by abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone started at week 10 from the start of the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.
Period Title: Overall Study
STARTED	35	34
Subjects Randomized (Efficacy Analysis)	35	34
Rcvd ≥1 Leukapheresis (Safety Analysis)	35	34
COMPLETED	16	15
NOT COMPLETED	19	19

Baseline Characteristics

Arm/Group Title	Concurrent Arm	Sequential Arm	Total
Arm/Group Description	Subjects received sipuleucel-T concurrent with abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone treatment started the next day after the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death, occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.	Subjects received sipuleucel-T therapy followed by abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone started at week 10 from the start of the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death, occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.	Total of all reporting groups
Overall Participants	35	34	69
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 37.1%	11 32.4%	24 34.8%
>=65 years	22 62.9%	23 67.6%	45 65.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.7 (9.8)	70.5 (10.15)	70.1 (9.91)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	35 100%	34 100%	69 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 5.9%	2 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 5.7%	3 8.8%	5 7.2%
White	33 94.3%	29 85.3%	62 89.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	35 100%	34 100%	69 100%
Weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	94.22 (21.38)	93.46 (16.29)	93.85 (18.90)
Height (Centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters]	176.10 (8.25)	177.39 (8.06)	176.73 (8.12)
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
ECOG 0=Fully Active; No restrictions	28 80%	26 76.5%	54 78.3%
ECOG 1= Restricted Strenuous Activity	7 20%	8 23.5%	15 21.7%
Gleason Score (Count of Participants)
Gleason Score ≤ 6	5 14.3%	5 14.7%	10 14.5%
Gleason Score = 7	12 34.3%	8 23.5%	20 29%
Gleason Score ≥ 8	18 51.4%	20 58.8%	38 55.1%
Gleason Score - Missing Data	0 0%	1 2.9%	1 1.4%

Outcome Measures

1. Primary Outcome

Title	Cumulative CD54 Upregulation Ratio Between the Cohorts.
Description	An analysis of variance model for the log transformed cumulative CD54 upregulation ratio (CD54 upregulation is the fold increase in the final product (FP) from buoyant density separations (BDS) step 65. BDS65 step refers to sample taken after both BDS77 and BDS65 but before ex vivo culture in the presence of antigen PA2024. FP refers to sample taken after ex vivo culture) that includes the antigen concentration cohort as the independent variable was performed. Subjects who received all 3 infusions were included.
Time Frame	Over the course of sipuleucel-T therapy (approximately 1 month)

Outcome Measure Data

Analysis Population Description

The efficacy population is defined as all randomized subjects. All the subjects in the efficacy population were analyzed according to the treatment that they were randomized to receive.

Arm/Group Title	Concurrent Arm	Sequential Arm
Arm/Group Description	Subjects received sipuleucel-T concurrent with abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone treatment started the next day after the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.	Subjects received sipuleucel-T therapy followed by abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone started at week 10 from the start of the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.
Measure Participants	35	34
Mean (Standard Error) [Ratio ofCD54 molecules on BDS65:FP cells]	36.72 (2.32)	41.61 (2.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concurrent Arm, Sequential Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2141
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Wilcoxon rank-sum test.

Adverse Events

Time Frame	All adverse events (AEs) and serious adverse events (SAEs) were recorded from registration until the Post-Treatment Visit (30-37 days after last study treatment). Only treatment-related AEs and cerebrovascular events (CVEs) ongoing at the Post-Treatment Visit, were followed until resolution, return to baseline or no further improvement was expected. After the Post-Treatment Visit, only new treatment-related SAEs and CVEs (regardless of causality) were collected and recorded as SAEs.
Arm/Group Title	Concurrent Arm		Sequential Arm
Arm/Group Description	Subjects received sipuleucel-T concurrent with abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone treatment started the next day after the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.		Subjects received sipuleucel-T therapy followed by abiraterone acetate plus prednisone. Abiraterone acetate plus prednisone started at week 10 from the start of the first infusion of sipuleucel-T and continued for 26 weeks or until disease progression, unacceptable toxicity, or death occurred. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). abiraterone acetate: Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.
All Cause Mortality
	Concurrent Arm		Sequential Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/35 (54.3%)		19/34 (55.9%)
Serious Adverse Events
	Concurrent Arm		Sequential Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/35 (20%)		14/34 (41.2%)
Blood and lymphatic system disorders
Anaemia	0/35 (0%)	0	1/34 (2.9%)	1
Cardiac disorders
Sinus tachycardia	0/35 (0%)	0	1/34 (2.9%)	1
Gastrointestinal disorders
Diarrhoea	1/35 (2.9%)	1	0/34 (0%)	0
Rectal Haemorrhage	0/35 (0%)	0	1/34 (2.9%)	1
General disorders
Disease Progression	1/35 (2.9%)	1	2/34 (5.9%)	2
Asthenia	0/35 (0%)	0	1/34 (2.9%)	1
Chest Pain	0/35 (0%)	0	1/34 (2.9%)	1
Systemic Inflammatory Response Syndrome	0/35 (0%)	0	1/34 (2.9%)	1
Infections and infestations
Cystitis	0/35 (0%)	0	1/34 (2.9%)	1
Influenza	0/35 (0%)	0	1/34 (2.9%)	1
Sepsis	0/35 (0%)	0	1/34 (2.9%)	1
Urosepsis	1/35 (2.9%)	1	0/34 (0%)	0
Injury, poisoning and procedural complications
Subdural Haematoma	1/35 (2.9%)	1	0/34 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/35 (0%)	0	1/34 (2.9%)	1
Hypokalaemia	0/35 (0%)	0	1/34 (2.9%)	1
Musculoskeletal and connective tissue disorders
Muscle Haemorrhage	0/35 (0%)	0	1/34 (2.9%)	1
Pathological Fracture	1/35 (2.9%)	1	0/34 (0%)	0
Nervous system disorders
Syncope	0/35 (0%)	0	2/34 (5.9%)	2
Cerebrovascular Accident	1/35 (2.9%)	1	0/34 (0%)	0
Haemorrhage Intracranial	0/35 (0%)	0	1/34 (2.9%)	1
Renal and urinary disorders
Haematuria	0/35 (0%)	0	1/34 (2.9%)	1
Obstructive Uropathy	0/35 (0%)	0	1/34 (2.9%)	1
Renal Failure	0/35 (0%)	0	1/34 (2.9%)	1
Ureteric Obstruction	0/35 (0%)	0	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/35 (2.9%)	1	0/34 (0%)	0
Respiratory Distress	0/35 (0%)	0	1/34 (2.9%)	1
Vascular disorders
Hypertensive Crisis	0/35 (0%)	0	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Concurrent Arm		Sequential Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/35 (100%)		32/34 (94.1%)
Blood and lymphatic system disorders
Anaemia	2/35 (5.7%)	2	7/34 (20.6%)	12
Ear and labyrinth disorders
Vertigo	2/35 (5.7%)	2	1/34 (2.9%)	1
Gastrointestinal disorders
Nausea	8/35 (22.9%)	9	10/34 (29.4%)	12
Paraesthesia Oral	8/35 (22.9%)	12	7/34 (20.6%)	14
Constipation	4/35 (11.4%)	4	7/34 (20.6%)	8
Diarrhoea	6/35 (17.1%)	7	3/34 (8.8%)	5
Vomiting	3/35 (8.6%)	3	5/34 (14.7%)	6
Abdominal Pain	2/35 (5.7%)	2	3/34 (8.8%)	3
Dyspepsia	1/35 (2.9%)	1	3/34 (8.8%)	4
Flatulence	2/35 (5.7%)	2	1/34 (2.9%)	1
Abdominal Distension	0/35 (0%)	0	2/34 (5.9%)	2
General disorders
Fatigue	10/35 (28.6%)	10	9/34 (26.5%)	17
Oedema Periperal	10/35 (28.6%)	12	5/34 (14.7%)	6
Chills	6/35 (17.1%)	9	8/34 (23.5%)	12
Pyrexia	7/35 (20%)	7	5/34 (14.7%)	8
Pain	1/35 (2.9%)	1	7/34 (20.6%)	8
Influenza Like Illness	1/35 (2.9%)	1	5/34 (14.7%)	8
Asthenia	3/35 (8.6%)	3	2/34 (5.9%)	2
Gait Disturbance	1/35 (2.9%)	1	3/34 (8.8%)	3
Chest Pain	0/35 (0%)	0	3/34 (8.8%)	4
Oedema	2/35 (5.7%)	2	0/34 (0%)	0
Infections and infestations
Nasopharyngitis	2/35 (5.7%)	2	2/34 (5.9%)	3
Urinary Tract Infection	3/35 (8.6%)	3	1/34 (2.9%)	1
Bronchitis	1/35 (2.9%)	1	2/34 (5.9%)	2
Influenza	0/35 (0%)	0	2/34 (5.9%)	2
Oral Herpes	0/35 (0%)	0	2/34 (5.9%)	2
Injury, poisoning and procedural complications
Citrate Toxicity	3/35 (8.6%)	8	6/34 (17.6%)	12
Contusion	3/35 (8.6%)	3	2/34 (5.9%)	3
Fall	1/35 (2.9%)	1	4/34 (11.8%)	4
Procedural Pain	0/35 (0%)	0	2/34 (5.9%)	2
Investigations
Blood Alkaline Phosphatase Increased	0/35 (0%)	0	3/34 (8.8%)	3
Blood Urea Increased	0/35 (0%)	0	2/34 (5.9%)	2
Heart Rate Irregular	2/35 (5.7%)	2	0/34 (0%)	0
Weight Decreased	0/35 (0%)	0	2/34 (5.9%)	2
Metabolism and nutrition disorders
Decreased Appetite	1/35 (2.9%)	1	4/34 (11.8%)	4
Dehydration	1/35 (2.9%)	1	3/34 (8.8%)	3
Hypokalaemia	1/35 (2.9%)	1	3/34 (8.8%)	3
Hyperglycaemia	3/35 (8.6%)	3	0/34 (0%)	0
Hyponatraemia	2/35 (5.7%)	2	0/34 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	17/35 (48.6%)	22	9/34 (26.5%)	14
Back Pain	6/35 (17.1%)	6	10/34 (29.4%)	10
Arthralgia	6/35 (17.1%)	7	7/34 (20.6%)	9
Pain in Extremity	3/35 (8.6%)	3	8/34 (23.5%)	11
Musculoskeletal Chest Pain	4/35 (11.4%)	5	3/34 (8.8%)	3
Musculoskeletal Pain	4/35 (11.4%)	6	2/34 (5.9%)	5
Myalgia	3/35 (8.6%)	5	3/34 (8.8%)	5
Bone Pain	1/35 (2.9%)	1	3/34 (8.8%)	3
Muscular Weakness	2/35 (5.7%)	2	1/34 (2.9%)	1
Flank Pain	0/35 (0%)	0	2/34 (5.9%)	2
Nervous system disorders
Paraesthesia	5/35 (14.3%)	6	6/34 (17.6%)	8
Headache	5/35 (14.3%)	5	5/34 (14.7%)	6
Dizziness	2/35 (5.7%)	2	6/34 (17.6%)	9
Hypoaesthesia	2/35 (5.7%)	2	4/34 (11.8%)	4
Tremor	1/35 (2.9%)	1	3/34 (8.8%)	3
Dysgeusia	1/35 (2.9%)	1	2/34 (5.9%)	3
Syncope	0/35 (0%)	0	2/34 (5.9%)	3
Psychiatric disorders
Anxiety	3/35 (8.6%)	3	1/34 (2.9%)	1
Insomnia	1/35 (2.9%)	1	3/34 (8.8%)	3
Depression	0/35 (0%)	0	3/34 (8.8%)	4
Renal and urinary disorders
Pollakiuria	2/35 (5.7%)	2	3/34 (8.8%)	3
Haematuria	1/35 (2.9%)	1	2/34 (5.9%)	2
Dysuria	0/35 (0%)	0	2/34 (5.9%)	2
Hydronephrosis	0/35 (0%)	0	2/34 (5.9%)	3
Reproductive system and breast disorders
Gynaecomastia	2/35 (5.7%)	2	2/34 (5.9%)	2
Respiratory, thoracic and mediastinal disorders
Cough	9/35 (25.7%)	10	7/34 (20.6%)	10
Dyspnoea	3/35 (8.6%)	3	5/34 (14.7%)	7
Nasal Congestion	2/35 (5.7%)	2	2/34 (5.9%)	2
Epistaxis	0/35 (0%)	0	2/34 (5.9%)	2
Hypoxia	0/35 (0%)	0	2/34 (5.9%)	2
Pleuritic Pain	2/35 (5.7%)	2	0/34 (0%)	0
Skin and subcutaneous tissue disorders
Ecchymosis	4/35 (11.4%)	6	4/34 (11.8%)	5
Hyperhidrosis	1/35 (2.9%)	1	3/34 (8.8%)	3
Vascular disorders
Hot Flush	5/35 (14.3%)	5	3/34 (8.8%)	3
Hypertension	4/35 (11.4%)	4	4/34 (11.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The results of the Study will be published and/or presented in an integrated manner reflecting the results observed across all participating centers. Accordingly, decisions on timing and content of publications and presentations relating to the Study will be coordinated by Dendreon in communication with institutions contributing patients to the Study.