Abiraterone Acetate and Antiandrogen Therapy With or With... | NCT03419234

ID	Type	Description	Link
NCI-2017-00389	Registry Identifier	CTRP (Clinical Trial Reporting Program)
EA8153	Other Identifier	ECOG-ACRIN Cancer Research Group
EA8153	Other Identifier	CTEP
U10CA180820	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with castration-resistant prostate cancer (CRPC) that have previously received docetaxel and androgen deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) can improve progression-free survival (PFS) compared to abiraterone acetate alone.

SECONDARY OBJECTIVES:

I. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel and ADT for HSPC can increase the percentage of change in prostate-specific antigen (PSA) from baseline to week 12 of treatment as well as the maximum decline in PSA that occurs at any point after treatment compared to abiraterone acetate alone.

II. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel for HSPC can prolong time to PSA progression compared to abiraterone acetate alone.

III. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel for HSPC can improve radiographic response (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) compared to abiraterone acetate alone.

IV. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel and ADT for HSPC can prolong the overall survival (OS) compared to abiraterone acetate alone.

V. To assess safety and tolerability of the combination of 6 cycles of cabazitaxel and abiraterone acetate.

TERTIARY OBJECTIVES:

I. To examine whether patients with circulating tumor cells (CTCs) positive for AR-V7 at baseline have a longer radiographic or clinical PFS to the combination of cabazitaxel and abiraterone acetate vs. abiraterone acetate alone.

II. To examine whether the addition of cabazitaxel to abiraterone acetate can change the AR-V7 status of patients who are positive at study entry.

III. To examine whether the addition of cabazitaxel to abiraterone acetate has any impact on future development of AR-V7 positivity at the time of disease progression.

IV. To assess if the changes in total tumor burden from baseline to week 12 as assessed with sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) will differ between two arms.

V. To correlate total tumor burden at the baseline as assessed with NaF PET/CT with the PFS.

VI. To correlate heterogeneity of response from baseline to week 12 as assessed with NaF PET/CT with the PFS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive abiraterone acetate orally (PO) once daily (QD) on days 1-21, prednisone PO twice daily (BID) on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel intravenously (IV) over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or surgical castration with bilateral orchiectomy.

ARM B: Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

After completion of study treatment, patients are followed up every 3 or 6 months and then annually for up to 5 years.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (abiraterone acetate, prednisone, cabazitaxel)	Experimental	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.	Drug: Abiraterone Acetate Drug: Androgen deprivation therapy Drug: Cabazitaxel Drug: Prednisone
Arm B (abiraterone acetate, prednisone)	Active Comparator	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.	Drug: Abiraterone Acetate Drug: Androgen deprivation therapy Drug: Prednisone

Name	Type	Description	Arm Group Labels	Other Names
Abiraterone Acetate	Drug	Given PO	Arm A (abiraterone acetate, prednisone, cabazitaxel) Arm B (abiraterone acetate, prednisone)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as time from randomization to radiographic progression, symptomatic deterioration requiring discontinuation of treatment or death, whichever occurs first. Patients who died without documented radiographic progression or symptomatic deterioration and the death occurred more than 6.5 months after the date of last disease assessment were censored at the date of last disease assessment.	Assessed every 9 weeks for the first 18 weeks, then every 12 weeks until treatment discontinuation; if treatment discontinued prior to radiographic progression, then every 3 months until radiographic progression, up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Percent Change in PSA From Baseline to 12 Weeks	PSA was assessed at baseline and 12 weeks. Percent change in PSA from baseline to 12 weeks is calculated as follows: ((PSA at 12 weeks - baseline PSA)/baseline PSA) x 100	Assessed at baseline and 12 weeks
Maximum Percent Change in PSA From Baseline While on Treatment

Other Outcomes

Measure	Description	Time Frame
PFS Among Patients With Circulating Tumor Cells (CTCs) Positive for Androgen-receptor Splice Variant 7 Messenger RNA (AR-V7) at Baseline	PFS is defined as time from randomization to radiographic progression, symptomatic deterioration requiring discontinuation of treatment or death, whichever occurs first. Patients who died without documented radiographic progression or symptomatic deterioration and the death occurred more than 6.5 months after the date of last disease assessment were censored at the date of last disease assessment. AR-V7 was assessed at baseline.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
Previous chemotherapy with at least 3 cycles of docetaxel for hormone-sensitive metastatic prostate cancer
Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT/magnetic resonance imaging [MRI] of abdomen/pelvis, bone scintigraphy or NaF PET/CT)
Ability to swallow abiraterone acetate tablets as a whole
All patients must be receiving standard of care androgen deprivation treatment (surgical castration versus LHRH agonist or antagonist treatment); subjects receiving LHRH agonist or antagonist must continue treatment throughout the time on this study
Patients must have castrate serum level of testosterone of < 50 ng/dL (< 1.73 nmol/L)
Patients must have progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for PSA, measurable disease or non-measurable (bone) disease during treatment with ADT:
- PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value >= 1.0 ng/mL, confirmed <=4 weeks prior to randomization
- Measurable disease (by RECIST 1.1): > 20% increase in the sum of the longest diameters of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be more than 15 mm to be assessed for change in size
- Non-measurable (bone) disease: The appearance of two or more new areas of uptake on bone scan (or NaF PET/CT) consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI). Clinical decisions about response or progression will be based on CT and bone scans.
Patients may or may not have been treated previously with a nonsteroidal antiandrogen, such as flutamide, bicalutamide or nilutamide; for patients previously treated with an antiandrogen, they must be off treatment for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration and must have shown PSA progression after discontinuing the anti-androgen
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Absolute neutrophil count (ANC) >= 1500/mm^3
Hemoglobin (HgB) >= 9.0 gr/dL
Platelets >= 100,000/mm^3
Creatinine < 2.0 mg/dL
Patients must be informed of the experimental nature of the study and its potential risks, and must sign an Institutional Review Board (IRB)-approved written informed consent form indicating such an understanding
Patients with resected or irradiated brain metastases or those treated with stereotactic radiation therapy are eligible to enroll, provided that they do not require treatment with steroids that exceeds 10 mg of prednisone daily or equivalent
Sexually active males must use an accepted and effective method of double barrier contraception or abstain from sexual intercourse for the duration of their participation in the study and for 26 weeks after the last dose of study drug
NaF PET/CT OPTIONAL SUB-STUDY ELIGIBILITY CRITERIA
- Ability to lie still for imaging
- Weight =< 300 lbs (pounds)
- Metastatic disease confined predominantly to the bones

Exclusion Criteria:

Any prior chemotherapy or androgen receptor (AR)-directed therapy for CRPC, (e.g. docetaxel, cabazitaxel, mitoxantrone, abiraterone acetate, ketoconazole, or enzalutamide); previous treatment with radium-223 or sipuleucel-T is allowed
Pure small cell or other variant (non-adenocarcinoma) prostate cancer histology for which treatment with abiraterone would not be considered appropriate
Patients may not be receiving other therapeutic investigational agents or be receiving concurrent anticancer therapy other than standard androgen deprivation therapy; concurrent treatment with agents to prevent skeletal-related events (such as zoledronic acid or denosumab) will be allowed as long as it was initiated prior to study entry or there are plans to initiate it after cycle 2 day 1.
Any medical condition for which prednisone (corticosteroid) is contraindicated
Total bilirubin > upper limit of normal (ULN) (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is > ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible)
Alanine (ALT) or aspartate (AST) aminotransferase > 1.5 x ULN
Active infection requiring treatment with antibiotics
History of adrenal insufficiency or hypoaldosteronism
Myocardial infarction or arterial thrombotic event within 6 months of randomization, heart failure of New York Heart Association class II or higher, uncontrolled angina, severe uncontrolled ventricular arrhythmia
External beam radiation therapy within 2 weeks of registration
Prior history of allergic reactions to G-CSF
Prior history of allergic reactions to docetaxel and/or to medications formulated with polysorbate 80
History of active malignancy; patients with a history of cancer that has been adequately treated and are free of disease recurrence for 3 years or more are allowed to participate; patients with non-melanoma skin cancers or carcinoma in situ of the bladder that have been adequately excised are eligible to participate
Life expectancy of < 12 months at screening
Grade >= 2 neuropathy
Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg). Patients with a history of hypertension are allowed to enroll provided blood pressure is controlled with anti-hypertensive treatment

Name	Affiliation	Role
Christos Kyriakopoulos	ECOG-ACRIN Cancer Research Group	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Fairbanks Memorial Hospital		Fairbanks	Alaska	99701	United States
CTCA at Western Regional Medical Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Sep 17, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS)

PFS is defined as time from randomization to radiographic progression, symptomatic deterioration requiring discontinuation of treatment or death, whichever occurs first. Patients who died without documented radiographic progression or symptomatic deterioration and the death occurred more than 6.5 months after the date of last disease assessment were censored at the date of last disease assessment.

All randomized patients are included in this analysis.

Posted

Median

95% Confidence Interval

months

Assessed every 9 weeks for the first 18 weeks, then every 12 weeks until treatment discontinuation; if treatment discontinued prior to radiographic progression, then every 3 months until radiographic progression, up to 5 years

ID	Title	Description
OG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy. Abiraterone Acetate: Given PO Androgen deprivation therapy: Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist or surgical castration with bilateral orchiectomy. Cabazitaxel: Given IV Prednisone: Given PO
OG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy. Abiraterone Acetate: Given PO Androgen deprivation therapy: Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist or surgical castration with bilateral orchiectomy. Prednisone: Given PO

Units	Counts
Participants	OG000111 OG001112

Title

Denominators

Categories

Title	Measurements
	OG00014.9(9.9 to 18.6) OG0019.9(7.0 to 12.6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank	Stratified log rank test	0.049														Superiority

Secondary

Percent Change in PSA From Baseline to 12 Weeks

PSA was assessed at baseline and 12 weeks. Percent change in PSA from baseline to 12 weeks is calculated as follows:

((PSA at 12 weeks - baseline PSA)/baseline PSA) x 100

Patients who started protocol therapy and had both baseline PSA as well as 12-week PSA available are included in this analysis.

Posted

Median

Inter-Quartile Range

percentage of change in PSA

Assessed at baseline and 12 weeks

ID	Title	Description
OG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
OG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

Secondary

Maximum Percent Change in PSA From Baseline While on Treatment

Maximum percent change in PSA from baseline while on treatment was calculated as follows:

((PSA nadir while on treatment - baseline PSA)/baseline PSA) x 100

Patients who started protocol therapy are included in this analysis.

Posted

Median

Inter-Quartile Range

percentage of change in PSA

Assessed at baseline, every 3 weeks for 18 weeks, then every 6 weeks until treatment discontinuation, up to 5 years

ID	Title	Description
OG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
OG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

Secondary

Time to PSA Progression

Time to PSA progression was defined as the time from randomization to PSA progression or date of last PSA assessment. Patients who experienced radiographic progression without documented PSA progression were counted as having an event.

All randomized patients are included in this analysis.

Posted

Median

95% Confidence Interval

months

Assessed at baseline, every 3 weeks for 18 weeks, then every 6 weeks until treatment discontinuation, up to 5 years

ID	Title	Description
OG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
OG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

Secondary

Proportion of Patients With Radiographic Response

Radiographic response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and was defined as either complete response (CR) or partial response (PR).

CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. All (non-target) lymph nodes must be non-pathological in size (< 10 mm short axis).

PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

All randomized patients are included in this analysis.

Posted

Number

95% Confidence Interval

Proportion of participants

ID	Title	Description
OG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy. Abiraterone Acetate: Given PO Androgen deprivation therapy: Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist or surgical castration with bilateral orchiectomy. Cabazitaxel: Given IV Prednisone: Given PO

Secondary

Overall Survival (OS)

Overall survival was defined as the time from randomization until death or date last known alive.

All randomized patients are included in this analysis.

Posted

Median

95% Confidence Interval

months

Assessed every 3 month is patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, and then annually for up to year 5

ID	Title	Description
OG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy. Abiraterone Acetate: Given PO Androgen deprivation therapy: Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist or surgical castration with bilateral orchiectomy. Cabazitaxel: Given IV Prednisone: Given PO
OG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy. Abiraterone Acetate: Given PO Androgen deprivation therapy: Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist or surgical castration with bilateral orchiectomy. Prednisone: Given PO

Other Pre-specified

PFS Among Patients With Circulating Tumor Cells (CTCs) Positive for Androgen-receptor Splice Variant 7 Messenger RNA (AR-V7) at Baseline

Not Posted

Assessed at baseline, every 9 weeks for the first 18 weeks, then every 12 weeks until treatment discontinuation; if treatment discontinued prior to radiographic progression, then every 3 months until radiographic progression, up to 5 years

Participants

Other Pre-specified

Androgen-Receptor Splice Variant 7 Messenger RNA (AR-V7) Status

The presence of AR-V7 in circulating tumor cells was assessed at baseline and Cycle 5 Day 1.

Not Posted

Assessed at baseline and Cycle 5 Day 1

Participants

Other Pre-specified

Development of AR-V7 Positivity at the Time of Disease Progression

The presence of AR-V7 in circulating tumor cells was assessed at baseline and disease progression.

Not Posted

Assessed at baseline and disease progression

Participants

Other Pre-specified

Changes in Total Tumor Burden From Baseline to Week 12 as Assessed With NaF PET/CT

Total tumor burden was assessed by NaF PET/CT at baseline and 12 weeks. The changes in total tumor burden will be compared between the two arms.

Not Posted

Assessed at baseline and 12 weeks

Participants

Other Pre-specified

Association Between PFS and Total Tumor Burden at the Baseline as Assessed With NaF PET/CT

Not Posted

Participants

Other Pre-specified

The Association Between PFS and the Heterogeneity of Response From Baseline to Week 12 as Assessed With NaF PET/CT

Not Posted

Assessed at baseline, 12 weeks, every 9 weeks for the first 18 weeks, then every 12 weeks until treatment discontinuation; if treatment discontinued prior to radiographic progression, then every 3 months until radiographic progression, up to 5 years

Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE 5.0	Systematic Assessment	EG0007 affected109 at risk EG0011 affected108 at risk
Febrile neutropenia	Blood and lymphatic system disorders	CTCAE 5.0	Systematic Assessment	EG0003 affected109 at risk EG0010 affected108 at risk
Atrial fibrillation	Cardiac disorders	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0011 affected108 at risk
Atrial flutter	Cardiac disorders	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0011 affected108 at risk
Fatigue	General disorders and administration site conditions	CTCAE 5.0	Systematic Assessment	EG0006 affected109 at risk EG0012 affected108 at risk
Fever	General disorders and administration site conditions	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0011 affected108 at risk
Colitis	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Diarrhea	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0004 affected109 at risk EG0010 affected108 at risk
Gastric hemorrhage	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Nausea	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Vomiting	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Bladder infection	Infections and infestations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Enterocolitis infectious	Infections and infestations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Kidney infection	Infections and infestations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Sepsis	Infections and infestations	CTCAE 5.0	Systematic Assessment	EG0004 affected109 at risk EG0010 affected108 at risk
Urinary tract infection	Infections and infestations	CTCAE 5.0	Systematic Assessment	EG0005 affected109 at risk EG0010 affected108 at risk
Alanine aminotransferase increased	Investigations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0015 affected108 at risk
Alkaline phosphatase increased	Investigations	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0012 affected108 at risk
Aspartate aminotransferase increased	Investigations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0012 affected108 at risk
Blood bilirubin increased	Investigations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0011 affected108 at risk
Lymphocyte count decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG0004 affected109 at risk EG0012 affected108 at risk
Lymphocyte count increased	Investigations	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Neutrophil count decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG00011 affected109 at risk EG0010 affected108 at risk
Platelet count decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG0002 affected109 at risk EG0010 affected108 at risk
White blood cell decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG0009 affected109 at risk EG0010 affected108 at risk
Investigations - Other, specify	Investigations	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0011 affected108 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0013 affected108 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG0004 affected109 at risk EG0014 affected108 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Hypophosphatemia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0013 affected108 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Systematic Assessment	EG0002 affected109 at risk EG0010 affected108 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0011 affected108 at risk
Bone pain	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Systematic Assessment	EG0002 affected109 at risk EG0010 affected108 at risk
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Syncope	Nervous system disorders	CTCAE 5.0	Systematic Assessment	EG0000 affected109 at risk EG0011 affected108 at risk
Psychiatric disorders - Other, specify	Psychiatric disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE 5.0	Systematic Assessment	EG0002 affected109 at risk EG0011 affected108 at risk
Acute kidney injury	Renal and urinary disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Hematuria	Renal and urinary disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Hematoma	Vascular disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk
Hypertension	Vascular disorders	CTCAE 5.0	Systematic Assessment	EG00011 affected109 at risk EG00112 affected108 at risk
Hypotension	Vascular disorders	CTCAE 5.0	Systematic Assessment	EG0001 affected109 at risk EG0010 affected108 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE 5.0	Systematic Assessment	EG00060 affected109 at risk EG00130 affected108 at risk
Edema limbs	General disorders and administration site conditions	CTCAE 5.0	Systematic Assessment	EG00022 affected109 at risk EG00113 affected108 at risk
Fatigue	General disorders and administration site conditions	CTCAE 5.0	Systematic Assessment	EG00078 affected109 at risk EG00147 affected108 at risk
Constipation	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG00012 affected109 at risk EG0018 affected108 at risk
Diarrhea	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG00037 affected109 at risk EG0016 affected108 at risk
Nausea	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG0006 affected109 at risk EG0012 affected108 at risk
Vomiting	Gastrointestinal disorders	CTCAE 5.0	Systematic Assessment	EG00018 affected109 at risk EG0014 affected108 at risk
Urinary tract infection	Infections and infestations	CTCAE 5.0	Systematic Assessment	EG0007 affected109 at risk EG0012 affected108 at risk
Lymphocyte count decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG00014 affected109 at risk EG0013 affected108 at risk
Neutrophil count decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG0008 affected109 at risk EG0011 affected108 at risk
White blood cell decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG0007 affected109 at risk EG0011 affected108 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG0007 affected109 at risk EG0011 affected108 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE 5.0	Systematic Assessment	EG00019 affected109 at risk EG00119 affected108 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE 5.0	Systematic Assessment	EG0006 affected109 at risk EG0011 affected108 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE 5.0	Systematic Assessment	EG00012 affected109 at risk EG0019 affected108 at risk
Hypertension	Vascular disorders	CTCAE 5.0	Systematic Assessment	EG00037 affected109 at risk EG00136 affected108 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D000069501	Abiraterone Acetate
D000726	Androgen Antagonists
C552428	cabazitaxel
C532412	XRP6258
D011241	Prednisone

ID	Term
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes

ID	Title	Description
BG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
BG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A (Abiraterone Acetate, Prednisone, Cabazitaxel)	Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.	80	111	46	109	101	109
EG001	Arm B (Abiraterone Acetate, Prednisone)	Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.	79	112	31	108	80	108