Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01576172
• Collaborator: (none)
• Enrollment: 159
• Locations: 14
• Arms: 2
• Actual Duration (Months): 96.8
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This randomized phase II trial studies abiraterone acetate and prednisone together with veliparib to see how well it works compared to abiraterone acetate and prednisone alone in treating patients with castration-resistant prostate cancer that has spread from the primary site to other places in the body. Androgens can cause the growth of prostate cancer cells. Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abiraterone acetate together with prednisone and veliparib may work better than abiraterone acetate and prednisone alone in treating patients with castration-resistant prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Castration-Resistant Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer AJCC v7	Drug: Abiraterone Acetate; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Drug: Veliparib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the role of v-ets erythroblastosis virus E26 oncogene (ETS) gene fusion as a predictive biomarker for response to hormone therapy (abiraterone [abiraterone acetate]) alone or hormone therapy plus poly adenosine diphosphate-ribose polymerase 1 (PARP-1) targeted therapy (ABT-888 [veliparib]) in patients with metastatic castration resistant prostate cancer.

2. To evaluate whether the addition of PARP-1 targeted therapy is superior to hormone therapy alone based on ETS gene fusion status.

SECONDARY OBJECTIVES:

1. Rate of prostate-specific antigen (PSA) declines. II. Objective response rate. III. Progression-free survival. IV. Evaluate the qualitative and quantitative toxicity of abiraterone acetate with and without ABT-888.

TERTIARY OBJECTIVES:

1. To determine the concordance in fusion status among prostate cancer samples from the primary site, biopsied metastasis, and circulating tumor cells (CTCs).

2. To assess if ETS fusion status in the CTCs, at baseline, 12 weeks, and disease progression (or when off study) is associated with response to therapy.

3. To evaluate if the number of CTCs, as well as the expression levels of androgen receptor, RAD51 recombinase (RAD51), and gamma-H2A histone family, member X (H2aX) foci in the CTCs at baseline, at 12 weeks, and at disease progression in all patients is associated with response to therapy.

4. To determine the role of phosphatase and tensin homolog (PTEN) loss as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888.

5. To determine the role of PARP1 activity as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888.

6. To perform next-generation sequencing for discovery of novel gene fusions in prostate cancers negative for ETS fusions.

7. To perform germline single nucleotide polymorphism (SNP) analysis of genes involved in hormone synthesis, transport, binding, metabolism, and degradation for discovery of novel SNPs predictive of response to abiraterone, alone or in combination with ABT-888.

8. To determine if ETS fusion ribonucleic acid (RNA) levels in blood are predictive of response to abiraterone, alone or in combination with ABT-888.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive abiraterone acetate orally (PO) once daily (QD) and prednisone PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer
• Actual Study Start Date: Mar 30, 2012
• Actual Primary Completion Date: Oct 23, 2019
• Actual Study Completion Date: Apr 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (abiraterone acetate and prednisone) Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Abiraterone Acetate; Given PO; Other Names: CB7630 Yonsa Zytiga ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort Perrigo Prednisone PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisone Intensol Prednisonum Prednitone Promifen Rayos Servisone SK-Prednisone
Experimental: Arm II (abiraterone acetate, prednisone, and veliparib) Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Abiraterone Acetate; Given PO; Other Names: CB7630 Yonsa Zytiga ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort Perrigo Prednisone PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisone Intensol Prednisonum Prednitone Promifen Rayos Servisone SK-Prednisone ; Drug: Veliparib; Given PO; Other Names: ABT-888 PARP-1 inhibitor ABT-888

Outcome Measures

Primary Outcome Measures

1. Confirmed Prostate-specific Antigen (PSA) Response Rate [Up to 3 years]

   50% or greater decline in PSA from baseline.

Secondary Outcome Measures

1. Rates of PSA Decline [12 weeks]

   Change in PSA from baseline to 12 weeks

2. Objective Response Rates in Patients With Measurable Disease. [Up to 3 years]

   Overall response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

3. Progression-free Survival (PFS) [Up to 42 months]

   Time from randomization to disease progression or death.

4. Grade 4 or 5 Adverse Events [30 days after completion of study treatment]

   Grade 4 or greater toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 at least possibly related to treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a histologic or cytologic diagnosis of prostate cancer

• Have progressive metastatic castration-resistant prostate cancer, on androgen-deprivation therapy, based on at least one of the following criteria:

• PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval with a minimum PSA of 2 ng/mL

• Progression of bidimensionally measurable soft tissue (nodal metastasis) assessed within one month prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis

• Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan

• Agree to undergo a biopsy of at least 1 metastatic site for gene-fusion status analysis; adequate archival metastatic tissue can be used if available in lieu of a biopsy; patients will only be eligible for protocol therapy if the biopsy has tumor and the tissue is evaluable for ETS fusion status

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Have testosterone < 50 ng/dL; patients must continue primary androgen-deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy

• Patients must discontinue antiandrogen therapy for at least 4 weeks (e.g. flutamide, bicalutamide, nilutamide) prior to registration with no evidence of a falling PSA after washout; patients on steroids are eligible as long as they will be switched to prednisone

• Have no prior exposure to cytochrome 450 family 17(CYP-17) (other than ketoconazole) or PARP inhibitors for prostate cancer; patients with prior exposure to ketoconazole are eligible

• Patients with up to 2 prior chemotherapy regimens are eligible

• Obtained within 14 days prior to registration: White blood cells (WBC) >= 3,000/ul

• Obtained within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1,500/ul

• Obtained within 14 days prior to registration: Platelet count >= 100,000/ul

• Obtained within 14 days prior to registration: Serum creatinine =< 1.5 x the institutional upper limits of normal or corrected creatinine clearance of >= 50 mg/ml/hr/1.73 m^2 body surface area (BSA)

• Obtained within 14 days prior to registration: Potassium >= 3.5 mmol/L

• Obtained within 14 days prior to registration: Bilirubin within the institutional limits of normal

• Obtained within 14 days prior to registration: Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 times upper limit of normal

• Obtained within 14 days prior to registration: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 times upper limit of normal

• Measured within 28 days prior to administration of ABT-888: >= 10.0 g/dL hemoglobin (Hb) with no blood transfusion in the past 28 days

• Men must agree to use effective contraception during treatment and for at least 1 week after the last administration of therapy

• Patients must be able to take oral medication without crushing, dissolving, or chewing tablets

• Patients may have received prior radiation therapy or surgery; however, at least 21 days must have elapsed since completion of radiation therapy or surgery and patient must have recovered from all side effects at the time of registration

• Ability to understand and the willingness to sign a written informed-consent document that is approved by the local institutional review board

Exclusion Criteria:

• Patients may not be receiving any other investigational agents; any prior investigational products must be stopped at least 14 days (2-week washout) prior to registration

• Patients who have had chemotherapy, radiotherapy or oral antifungal agents (ketoconazole, itraconazole, fluconazole) within 3 weeks prior to entering the study or those who have not recovered (e.g. back to baseline or grade 1) from adverse events due to agents administered more than 3 weeks earlier

• There is a potential drug interaction when abiraterone is concomitantly used with a cytochrome P450 family 2, subfamily D, polypeptide 6 (CYP2D6) substrate narrow therapeutic index (e.g., thioridazine, dextromethorphan), or strong cytochrome P450 family 3, subfamily A, polypeptide 4 [CYP3A4] inhibitors (e.g., atazanavir, erythromycin, indinavir, itraconazole, Ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) or strong inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine); caution should be used when patients are on one of these drugs

• Patients with history of active seizures are not eligible

• Patients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, or chronic liver disease are not eligible

• Patients with known brain metastases should be excluded from this clinical trial

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or abiraterone

• Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St John's wort, etc.) must be discontinued before registration; patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment; hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) are forbidden during the trial and must be stopped prior to registration; no washout period will be required for any of these agents; patients on megestrol acetate for hot flashes are allowed to continue therapy

• Patients on stable doses of bisphosphonates or denosumab which have been started prior to registration may continue on this medication, patients who are not on bisphosphonates or denosumab are eligible as long as they initiate therapy prior to registration

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction

• Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible; patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

• Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS. Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	City of Hope South Pasadena	South Pasadena	California	United States	91030
4	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
5	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
6	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
7	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
8	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
9	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
10	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
11	M D Anderson Cancer Center	Houston	Texas	United States	77030
12	University of Washington Medical Center	Seattle	Washington	United States	98195
13	University of Wisconsin Women's Health Center	Madison	Wisconsin	United States	53715
14	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Maha H Hussain, University of Chicago Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 24, 2018

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01576172
• Other Study ID Numbers: NCI-2012-01149; NCI-2012-01149; NCI-2012-01919; 12-0109; CDR0000730114; UCCRC-IL057; 9012; 9012; N01CM00038; N01CM00039; N01CM00071; P30CA014599; P50CA097186; U01CA062491; U01CA070095; UM1CA186691; UM1CA186705; UM1CA186716
• First Posted: Apr 12, 2012
• Last Update Posted: Nov 12, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Carcinoma; Prostatic Neoplasms; Prednisone; Cortisone; Abiraterone Acetate; Veliparib

Study Results

Participant Flow

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Veliparib: Given PO
Period Title: Overall Study
STARTED	79	80
COMPLETED	74	79
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)	Total
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO Veliparib: Given PO	Total of all reporting groups
Overall Participants	74	79	153
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69	68	68
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	74 100%	79 100%	153 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.7%	2 2.5%	4 2.6%
Native Hawaiian or Other Pacific Islander	1 1.4%	0 0%	1 0.7%
Black or African American	9 12.2%	3 3.8%	12 7.8%
White	61 82.4%	74 93.7%	135 88.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.4%	0 0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Confirmed Prostate-specific Antigen (PSA) Response Rate
Description	50% or greater decline in PSA from baseline.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

2 patients non-evaluable in Arm I and 3 patients non-evaluable in Arm II due to receiving <2 treatment cycles

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO Veliparib: Given PO
Measure Participants	72	76
Count of Participants [Participants]	46 62.2%	55 69.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Abiraterone Acetate and Prednisone), Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Rates of PSA Decline
Description	Change in PSA from baseline to 12 weeks
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

3 patients in Arm 1 and 13 patients in Arm 2 had missing data.

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Veliparib: Given PO
Measure Participants	71	66
Mean (Standard Error) [ng/ml]	-41.1 (15.7)	-52.9 (26.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Abiraterone Acetate and Prednisone), Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	t-test, 2 sided
	Comments	t=-0.39 on 112.7 degrees of freedom (Satterthwaite)

3. Secondary Outcome

Title	Objective Response Rates in Patients With Measurable Disease.
Description	Overall response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Subset of patients with measurable disease.

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO Veliparib: Given PO
Measure Participants	40	46
Count of Participants [Participants]	18 24.3%	24 30.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Abiraterone Acetate and Prednisone), Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Time from randomization to disease progression or death.
Time Frame	Up to 42 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO Veliparib: Given PO
Measure Participants	72	76
Median (95% Confidence Interval) [months]	10.1	11.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Abiraterone Acetate and Prednisone), Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Grade 4 or 5 Adverse Events
Description	Grade 4 or greater toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 at least possibly related to treatment.
Time Frame	30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)	Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO	Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Prednisone: Given PO Veliparib: Given PO
Measure Participants	74	79
Count of Participants [Participants]	1 1.4%	3 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Abiraterone Acetate and Prednisone), Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	30 days after completion of study treatment (up to 42 months).
Adverse Event Reporting Description	Toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 without regard to attribution.
Arm/Group Title	Arm I (Abiraterone Acetate and Prednisone)		Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
Arm/Group Description	Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO		Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given PO Laboratory Biomarker Analysis: Correlative studies Prednisone: Given PO Veliparib: Given PO
All Cause Mortality
	Arm I (Abiraterone Acetate and Prednisone)		Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		1/79 (1.3%)
Serious Adverse Events
	Arm I (Abiraterone Acetate and Prednisone)		Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/74 (20.3%)		17/79 (21.5%)
Blood and lymphatic system disorders
Anemia	1/74 (1.4%)		1/79 (1.3%)
Cardiac disorders
Atrial fibrillation	0/74 (0%)		2/79 (2.5%)
Chest pain - cardiac	0/74 (0%)		1/79 (1.3%)
Heart failure	2/74 (2.7%)		0/79 (0%)
Myocardial infarction	1/74 (1.4%)		1/79 (1.3%)
Sinus tachycardia	0/74 (0%)		1/79 (1.3%)
Gastrointestinal disorders
Abdominal pain	0/74 (0%)		1/79 (1.3%)
Colonic obstruction	1/74 (1.4%)		0/79 (0%)
Nausea	0/74 (0%)		2/79 (2.5%)
Small intestinal obstruction	1/74 (1.4%)		0/79 (0%)
Vomiting	0/74 (0%)		3/79 (3.8%)
Dyspepsia	1/74 (1.4%)		0/79 (0%)
General disorders
General disorders and administration site conditions - Other, specify	1/74 (1.4%)		0/79 (0%)
Non-cardiac chest pain	1/74 (1.4%)		1/79 (1.3%)
Pain	0/74 (0%)		1/79 (1.3%)
Infections and infestations
Lung infection	1/74 (1.4%)		1/79 (1.3%)
Sepsis	0/74 (0%)		1/79 (1.3%)
Wound infection	0/74 (0%)		1/79 (1.3%)
Injury, poisoning and procedural complications
Fall	2/74 (2.7%)		1/79 (1.3%)
Hip fracture	1/74 (1.4%)		0/79 (0%)
Urostomy obstruction	0/74 (0%)		1/79 (1.3%)
Investigations
Platelet count decreased	0/74 (0%)		1/79 (1.3%)
Metabolism and nutrition disorders
Dehydration	0/74 (0%)		2/79 (2.5%)
Hyperglycemia	1/74 (1.4%)		1/79 (1.3%)
Hypoglycemia	1/74 (1.4%)		0/79 (0%)
Hypokalemia	1/74 (1.4%)		1/79 (1.3%)
Metabolism and nutrition disorders - Other, specify	0/74 (0%)		1/79 (1.3%)
Pain in extremity	1/74 (1.4%)		0/79 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/74 (1.4%)		0/79 (0%)
Nervous system disorders
Headache	0/74 (0%)		1/79 (1.3%)
Nervous system disorders - Other, specify	0/74 (0%)		1/79 (1.3%)
Presyncope	1/74 (1.4%)		1/79 (1.3%)
Stroke	0/74 (0%)		1/79 (1.3%)
Syncope	0/74 (0%)		1/79 (1.3%)
Psychiatric disorders
Confusion	0/74 (0%)		1/79 (1.3%)
Insomnia	0/74 (0%)		2/79 (2.5%)
Restlessness	0/74 (0%)		2/79 (2.5%)
Renal and urinary disorders
Cystitis noninfective	1/74 (1.4%)		0/79 (0%)
Renal calculi	0/74 (0%)		1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/74 (1.4%)		1/79 (1.3%)
Hypoxia	1/74 (1.4%)		0/79 (0%)
Pneumonitis	1/74 (1.4%)		0/79 (0%)
Respiratory, thoracic and mediastinal disorders - Other, specify	0/74 (0%)		1/79 (1.3%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/74 (1.4%)		0/79 (0%)
Vascular disorders
Hypertension	1/74 (1.4%)		1/79 (1.3%)
Hypotension	0/74 (0%)		1/79 (1.3%)
Thromboembolic event	2/74 (2.7%)		1/79 (1.3%)
Other (Not Including Serious) Adverse Events
	Arm I (Abiraterone Acetate and Prednisone)		Arm II (Abiraterone Acetate, Prednisone, and Veliparib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/74 (100%)		79/79 (100%)
Blood and lymphatic system disorders
Anemia	24/74 (32.4%)		26/79 (32.9%)
Gastrointestinal disorders
Abdominal pain	9/74 (12.2%)		5/79 (6.3%)
Constipation	9/74 (12.2%)		12/79 (15.2%)
Diarrhea	14/74 (18.9%)		15/79 (19%)
Dry mouth	1/74 (1.4%)		5/79 (6.3%)
Dyspepsia	1/74 (1.4%)		7/79 (8.9%)
Gastroesophageal reflux disease	4/74 (5.4%)		2/79 (2.5%)
Nausea	16/74 (21.6%)		47/79 (59.5%)
Vomiting	7/74 (9.5%)		18/79 (22.8%)
General disorders
Edema limbs	19/74 (25.7%)		8/79 (10.1%)
Fatigue	30/74 (40.5%)		44/79 (55.7%)
Non-cardiac chest pain	5/74 (6.8%)		2/79 (2.5%)
Pain	12/74 (16.2%)		21/79 (26.6%)
Infections and infestations
Sinusitis	4/74 (5.4%)		2/79 (2.5%)
Skin infection	2/74 (2.7%)		4/79 (5.1%)
Urinary tract infection	1/74 (1.4%)		7/79 (8.9%)
Injury, poisoning and procedural complications
Bruising	6/74 (8.1%)		14/79 (17.7%)
Fall	8/74 (10.8%)		7/79 (8.9%)
Investigations
Alanine aminotransferase increased	14/74 (18.9%)		7/79 (8.9%)
Alkaline phosphatase increased	19/74 (25.7%)		15/79 (19%)
Aspartate aminotransferase increased	17/74 (23%)		10/79 (12.7%)
Blood bilirubin increased	8/74 (10.8%)		5/79 (6.3%)
Creatinine increased	8/74 (10.8%)		8/79 (10.1%)
Lymphocyte count decreased	10/74 (13.5%)		20/79 (25.3%)
Platelet count decreased	12/74 (16.2%)		9/79 (11.4%)
Weight gain	8/74 (10.8%)		3/79 (3.8%)
Weight loss	9/74 (12.2%)		11/79 (13.9%)
White blood cell decreased	4/74 (5.4%)		7/79 (8.9%)
Metabolism and nutrition disorders
Anorexia	7/74 (9.5%)		12/79 (15.2%)
Hypercalcemia	6/74 (8.1%)		4/79 (5.1%)
Hyperglycemia	16/74 (21.6%)		23/79 (29.1%)
Hyperkalemia	11/74 (14.9%)		6/79 (7.6%)
Hypernatremia	6/74 (8.1%)		6/79 (7.6%)
Hypoalbuminemia	6/74 (8.1%)		7/79 (8.9%)
Hypocalcemia	7/74 (9.5%)		7/79 (8.9%)
Hypoglycemia	7/74 (9.5%)		5/79 (6.3%)
Hypokalemia	7/74 (9.5%)		11/79 (13.9%)
Hyponatremia	15/74 (20.3%)		9/79 (11.4%)
Hypophosphatemia	17/74 (23%)		14/79 (17.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/74 (4.1%)		7/79 (8.9%)
Back pain	23/74 (31.1%)		16/79 (20.3%)
Bone pain	14/74 (18.9%)		10/79 (12.7%)
Flank pain	4/74 (5.4%)		4/79 (5.1%)
Musculoskeletal and connective tissue disorder - Other, specify	0/74 (0%)		4/79 (5.1%)
Myalgia	2/74 (2.7%)		4/79 (5.1%)
Neck pain	4/74 (5.4%)		6/79 (7.6%)
Pain in extremity	28/74 (37.8%)		14/79 (17.7%)
Nervous system disorders
Dizziness	11/74 (14.9%)		16/79 (20.3%)
Dysgeusia	1/74 (1.4%)		4/79 (5.1%)
Headache	11/74 (14.9%)		14/79 (17.7%)
Peripheral sensory neuropathy	2/74 (2.7%)		4/79 (5.1%)
Paresthesia	4/74 (5.4%)		4/79 (5.1%)
Psychiatric disorders
Anxiety	3/74 (4.1%)		7/79 (8.9%)
Insomnia	10/74 (13.5%)		11/79 (13.9%)
Depression	5/74 (6.8%)		5/79 (6.3%)
Renal and urinary disorders
Cystitis noninfective	3/74 (4.1%)		6/79 (7.6%)
Hematuria	2/74 (2.7%)		7/79 (8.9%)
Urinary frequency	9/74 (12.2%)		16/79 (20.3%)
Urinary incontinence	5/74 (6.8%)		8/79 (10.1%)
Reproductive system and breast disorders
Pelvic pain	4/74 (5.4%)		1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Cough	14/74 (18.9%)		10/79 (12.7%)
Dyspnea	10/74 (13.5%)		12/79 (15.2%)
Nasal congestion	4/74 (5.4%)		8/79 (10.1%)
Productive cough	3/74 (4.1%)		4/79 (5.1%)
Upper respiratory infection	9/74 (12.2%)		9/79 (11.4%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	2/74 (2.7%)		5/79 (6.3%)
Skin and subcutaneous tissue disorders - Other, specify	5/74 (6.8%)		4/79 (5.1%)
Vascular disorders
Hot flashes	15/74 (20.3%)		24/79 (30.4%)
Hypertension	18/74 (24.3%)		15/79 (19%)
Hypotension	4/74 (5.4%)		0/79 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.