Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer
16 other identifiers
interventional
159
1 country
14
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2012
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 30, 2012
CompletedFirst Submitted
Initial submission to the registry
April 11, 2012
CompletedFirst Posted
Study publicly available on registry
April 12, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 23, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 23, 2020
CompletedResults Posted
Study results publicly available
November 12, 2020
CompletedNovember 12, 2020
October 1, 2020
7.6 years
April 11, 2012
October 21, 2020
October 21, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Confirmed Prostate-specific Antigen (PSA) Response Rate
50% or greater decline in PSA from baseline.
Up to 3 years
Secondary Outcomes (4)
Rates of PSA Decline
12 weeks
Objective Response Rates in Patients With Measurable Disease.
Up to 3 years
Progression-free Survival (PFS)
Up to 42 months
Grade 4 or 5 Adverse Events
30 days after completion of study treatment
Study Arms (2)
Arm I (abiraterone acetate and prednisone)
ACTIVE COMPARATORPatients 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.
Arm II (abiraterone acetate, prednisone, and veliparib)
EXPERIMENTALPatients 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.
Interventions
Given PO
Correlative studies
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- 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)
- +9 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
University of Wisconsin Women's Health Center
Madison, Wisconsin, 53715, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Related Publications (1)
Hussain M, Daignault-Newton S, Twardowski PW, Albany C, Stein MN, Kunju LP, Siddiqui J, Wu YM, Robinson D, Lonigro RJ, Cao X, Tomlins SA, Mehra R, Cooney KA, Montgomery B, Antonarakis ES, Shevrin DH, Corn PG, Whang YE, Smith DC, Caram MV, Knudsen KE, Stadler WM, Feng FY, Chinnaiyan AM. Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results From NCI 9012. J Clin Oncol. 2018 Apr 1;36(10):991-999. doi: 10.1200/JCO.2017.75.7310. Epub 2017 Dec 20.
PMID: 29261439DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Theodore Karrison, PhD
- Organization
- University of Chicago
Study Officials
- PRINCIPAL INVESTIGATOR
Maha H Hussain
University of Chicago Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2012
First Posted
April 12, 2012
Study Start
March 30, 2012
Primary Completion
October 23, 2019
Study Completion
April 23, 2020
Last Updated
November 12, 2020
Results First Posted
November 12, 2020
Record last verified: 2020-10